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BabyScreen+ newborn screening v1.114 ZNF674 Tommy Li Added phenotypes Mental retardation for gene: ZNF674
BabyScreen+ newborn screening v1.114 ZIC3 Tommy Li Added phenotypes X linked heterotaxy and congenital heart defects MIM:306955 for gene: ZIC3
BabyScreen+ newborn screening v1.114 YARS2 Tommy Li Added phenotypes Myopathy, lactic acidosis, and sideroblastic anemia for gene: YARS2
BabyScreen+ newborn screening v1.114 WDR62 Tommy Li Added phenotypes Microcephaly 2, primary, autosomal recessive, with or without cortical malformations MIM#604317 for gene: WDR62
BabyScreen+ newborn screening v1.114 VPS33B Tommy Li Added phenotypes Arthrogryposis, renal dysfunction, and cholestasis MIM#208085 for gene: VPS33B
Publications for gene VPS33B were updated from 15052268; 15052268; 18853461 to 15052268; 18853461
BabyScreen+ newborn screening v1.114 VLDLR Tommy Li Added phenotypes Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion MIM#224050 for gene: VLDLR
BabyScreen+ newborn screening v1.114 VIPAS39 Tommy Li Added phenotypes Arthrogryposis, renal dysfunction, and cholestasis MIM#613404 for gene: VIPAS39
BabyScreen+ newborn screening v1.114 VCP Tommy Li Added phenotypes Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia MIM#167320; Charcot-Marie-Tooth disease, type 2Y, MIM# 616687 for gene: VCP
BabyScreen+ newborn screening v1.114 UGT1A4 Tommy Li Added phenotypes Crigler-Najjar syndrome for gene: UGT1A4
BabyScreen+ newborn screening v1.114 UBR1 Tommy Li Added phenotypes Johanson-Blizzard syndrome MIM#243800 for gene: UBR1
BabyScreen+ newborn screening v1.114 UBA1 Tommy Li Added phenotypes Spinal muscular atrophy, X-linked infantile for gene: UBA1
BabyScreen+ newborn screening v1.114 TUBB4B Tommy Li Added phenotypes Leber congenital amaurosis with early-onset deafness MIM#617879 for gene: TUBB4B
BabyScreen+ newborn screening v1.114 TTR Tommy Li Added phenotypes Amyloidosis, hereditary, transthyretin-related MIM#105210 for gene: TTR
Publications for gene TTR were updated from 20301373; 3032328; 29972753; 29972757 to 3032328; 29972753; 29972757; 20301373
BabyScreen+ newborn screening v1.114 TSPEAR Tommy Li Added phenotypes Sensorineural deafness for gene: TSPEAR
BabyScreen+ newborn screening v1.114 TSEN54 Tommy Li Added phenotypes Pontocerebellar hypoplasia type 2A MIM#277470 for gene: TSEN54
BabyScreen+ newborn screening v1.114 TRPM2 Tommy Li Added phenotypes ALS and Parkinson's disease for gene: TRPM2
BabyScreen+ newborn screening v1.114 TRIM32 Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110 for gene: TRIM32
Publications for gene TRIM32 were updated from 21496629; 23142638 to 23142638; 21496629
BabyScreen+ newborn screening v1.114 TRAPPC2 Tommy Li Added phenotypes Spondyloepiphyseal dysplasia tarda MIM#313400 for gene: TRAPPC2
BabyScreen+ newborn screening v1.114 TPM2 Tommy Li Added phenotypes Arthrgryposis MIM#108120; Nemaline myopathy MIM#609285 for gene: TPM2
BabyScreen+ newborn screening v1.114 TNNT3 Tommy Li Added phenotypes Arthrogryposis, distal MIM#618435 for gene: TNNT3
BabyScreen+ newborn screening v1.114 TNNI2 Tommy Li Added phenotypes Arthrogryposis, distal, type 2B1 MIM#601680 for gene: TNNI2
BabyScreen+ newborn screening v1.114 TNFRSF13C Tommy Li Added phenotypes Immunodeficiency, common variable, 4 MIM#613494 for gene: TNFRSF13C
BabyScreen+ newborn screening v1.114 TNFRSF13B Tommy Li Added phenotypes Immunodeficiency, common variable, 2 MIM#240500 for gene: TNFRSF13B
BabyScreen+ newborn screening v1.114 TMPO Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: TMPO
BabyScreen+ newborn screening v1.114 TMEM43 Tommy Li Added phenotypes Arrhythmogenic right ventricular dysplasia 5 MIM#604400 for gene: TMEM43
Publications for gene TMEM43 were updated from 20301310; 34674311 to 34674311; 20301310
BabyScreen+ newborn screening v1.114 THRB Tommy Li Added phenotypes Thyroid hormone resistance, selective pituitary, MIM# 145650; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, MIM# 188570 for gene: THRB
BabyScreen+ newborn screening v1.114 THBS1 Tommy Li Added phenotypes Pulmonary hypertension for gene: THBS1
BabyScreen+ newborn screening v1.114 TFG Tommy Li Added phenotypes Spastic paraplegia 57, autosomal recessive, MIM# 615658; Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484 for gene: TFG
BabyScreen+ newborn screening v1.114 TFAP2B Tommy Li Added phenotypes Char syndrome, MIM 169100 for gene: TFAP2B
BabyScreen+ newborn screening v1.114 TCAP Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, type 2G; Cardiomyopathy, dilated for gene: TCAP
BabyScreen+ newborn screening v1.114 TBX20 Tommy Li Added phenotypes Congenital heart disease for gene: TBX20
BabyScreen+ newborn screening v1.114 TBX1 Tommy Li Added phenotypes DiGeorge syndrome MIM# 188400; Velocardiofacial syndrome MIM# 192430 for gene: TBX1
BabyScreen+ newborn screening v1.114 TBCE Tommy Li Added phenotypes Hypoparathyroidism retardation dysmorphism syndrome for gene: TBCE
BabyScreen+ newborn screening v1.114 TAZ Tommy Li Added phenotypes Barth syndrome, MIM#302060 for gene: TAZ
BabyScreen+ newborn screening v1.114 TARDBP Tommy Li Added phenotypes Amyotrophic lateral sclerosis type 10 for gene: TARDBP
BabyScreen+ newborn screening v1.114 TAB2 Tommy Li Added phenotypes Congenital heart disease, nonsyndromic for gene: TAB2
BabyScreen+ newborn screening v1.114 SYT14 Tommy Li Added phenotypes Spinocerebellar ataxia, autosomal recessive 11 for gene: SYT14
BabyScreen+ newborn screening v1.114 SYNE4 Tommy Li Added phenotypes Hearing loss for gene: SYNE4
BabyScreen+ newborn screening v1.114 SURF1 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, type 4K MIM#616684; Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110 for gene: SURF1
BabyScreen+ newborn screening v1.114 SRCAP Tommy Li Added phenotypes Floating-Harbor syndrome MIM#136140; Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, MIM# 619595 for gene: SRCAP
BabyScreen+ newborn screening v1.114 SPTLC2 Tommy Li Added phenotypes Neuropathy, hereditary sensory and autonomic, type IC for gene: SPTLC2
BabyScreen+ newborn screening v1.114 SPTB Tommy Li Added phenotypes Anaemia, neonatal haemolytic, fatal or near-fatal MIM# 617948 for gene: SPTB
BabyScreen+ newborn screening v1.114 SPEG Tommy Li Added phenotypes Centronuclear myopathy 5, MIM# 615959 for gene: SPEG
Publications for gene SPEG were updated from 26578207; 25087613; 30157964; 29614691; 28624463; 30412272; 31625632; 29474540 to 30412272; 26578207; 29474540; 31625632; 28624463; 30157964; 29614691; 25087613
BabyScreen+ newborn screening v1.114 SPARC Tommy Li Added phenotypes Osteogenesis imperfecta, type XVII, MIM# 616507 for gene: SPARC
BabyScreen+ newborn screening v1.114 SOX10 Tommy Li Added phenotypes Shah-Waardenburg syndrome for gene: SOX10
BabyScreen+ newborn screening v1.114 SNAP29 Tommy Li Added phenotypes Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome for gene: SNAP29
BabyScreen+ newborn screening v1.114 SMC1A Tommy Li Added phenotypes Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044; Cornelia de Lange syndrome 2, MIM# 300590 for gene: SMC1A
BabyScreen+ newborn screening v1.114 SMAD9 Tommy Li Added phenotypes Pulmonary arterial hypertension for gene: SMAD9
BabyScreen+ newborn screening v1.114 SMAD6 Tommy Li Added phenotypes Cardiovascular malformation, congenital for gene: SMAD6
BabyScreen+ newborn screening v1.114 SMAD1 Tommy Li Added phenotypes Pulmonary arterial hypertension for gene: SMAD1
BabyScreen+ newborn screening v1.114 SLCO2A1 Tommy Li Added phenotypes Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441 for gene: SLCO2A1
Publications for gene SLCO2A1 were updated from 22331663; 27134495; 33852188; 23509104 to 22331663; 27134495; 33852188; 23509104
BabyScreen+ newborn screening v1.114 SLC9A6 Tommy Li Added phenotypes Mental retardation, X-linked syndromic, Christianson type, MIM# 300243 for gene: SLC9A6
BabyScreen+ newborn screening v1.114 SLC6A19 Tommy Li Added phenotypes Hartnup disorder, MIM # 234500 for gene: SLC6A19
BabyScreen+ newborn screening v1.114 SLC4A4 Tommy Li Added phenotypes Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278 for gene: SLC4A4
BabyScreen+ newborn screening v1.114 SLC4A10 Tommy Li Added phenotypes Epilepsy & mental retardation for gene: SLC4A10
BabyScreen+ newborn screening v1.114 SLC34A2 Tommy Li Added phenotypes Pulmonary alveolar microlithiasis, MIM# 265100 for gene: SLC34A2
BabyScreen+ newborn screening v1.114 SLC33A1 Tommy Li Added phenotypes Congenital cataracts, hearing loss and low serum copper and ceruloplasmin; Spastic paraplegia, autosomal dominant for gene: SLC33A1
BabyScreen+ newborn screening v1.114 SLC2A10 Tommy Li Added phenotypes Arterial tortuosity syndrome MIM#208050 for gene: SLC2A10
BabyScreen+ newborn screening v1.114 SLC25A4 Tommy Li Added phenotypes Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418; Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184 for gene: SLC25A4
BabyScreen+ newborn screening v1.114 SLC25A22 Tommy Li Added phenotypes Early myoclonic encephalopathy for gene: SLC25A22
BabyScreen+ newborn screening v1.114 SLC16A12 Tommy Li Added phenotypes Cataract, juvenile with microcornea and renal glucosuria for gene: SLC16A12
BabyScreen+ newborn screening v1.114 SIL1 Tommy Li Added phenotypes Marinesco-Sjogren syndrome, MIM#248800 for gene: SIL1
BabyScreen+ newborn screening v1.114 SH3TC2 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, type 4C MIM#601596 for gene: SH3TC2
BabyScreen+ newborn screening v1.114 SGCG Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700 for gene: SGCG
BabyScreen+ newborn screening v1.114 SGCD Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287 for gene: SGCD
BabyScreen+ newborn screening v1.114 SGCB Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286 for gene: SGCB
BabyScreen+ newborn screening v1.114 SGCA Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099 for gene: SGCA
BabyScreen+ newborn screening v1.114 SFTPC Tommy Li Added phenotypes Surfactant metabolism dysfunction, pulmonary, 2, MIM# 610913 for gene: SFTPC
BabyScreen+ newborn screening v1.114 SFTPB Tommy Li Added phenotypes Surfactant metabolism dysfunction, pulmonary, 1, MIM# 265120 for gene: SFTPB
BabyScreen+ newborn screening v1.114 SFTPA2 Tommy Li Added phenotypes Pulmonary fibrosis, idiopathic for gene: SFTPA2
BabyScreen+ newborn screening v1.114 SETX Tommy Li Added phenotypes Spinocerebellar ataxia, autosomal recessive 1, 606002 for gene: SETX
BabyScreen+ newborn screening v1.114 SERPING1 Tommy Li Added phenotypes Angioedema, hereditary, 1 and 2 MIM#106100 for gene: SERPING1
BabyScreen+ newborn screening v1.114 SERPIND1 Tommy Li Added phenotypes Heparin cofactor 2 deficiency for gene: SERPIND1
BabyScreen+ newborn screening v1.114 SDHD Tommy Li Added phenotypes Mitochondrial complex II deficiency, nuclear type 3, MIM# 619167; Paragangliomas 1, with or without deafness, MIM# 168000 for gene: SDHD
BabyScreen+ newborn screening v1.114 SCO2 Tommy Li Added phenotypes Mitochondrial complex IV deficiency, nuclear type 2, MC4DN2, MIM#604377 for gene: SCO2
BabyScreen+ newborn screening v1.114 SCO1 Tommy Li Added phenotypes Hepatic failure, early onset, and neurologic disorder for gene: SCO1
BabyScreen+ newborn screening v1.114 SCN4A Tommy Li Added phenotypes Myasthenic syndrome, congenital, 16, MIM# 614198; Paramyotonia congenita , MIM#168300; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis, type 2, MIM# 170500; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Hypokalemic periodic paralysis, type 2, MIM# 613345 for gene: SCN4A
BabyScreen+ newborn screening v1.114 SCN3A Tommy Li Added phenotypes Epileptic encephalopathy, early infantile, 62, MIM# 617938 for gene: SCN3A
BabyScreen+ newborn screening v1.114 SCN1A Tommy Li Added phenotypes Developmental and epileptic encephalopathy 6B, non-Dravet , MIM#619317; Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM#604403 for gene: SCN1A
BabyScreen+ newborn screening v1.114 SCN11A Tommy Li Added phenotypes Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548 for gene: SCN11A
BabyScreen+ newborn screening v1.114 SCARB2 Tommy Li Added phenotypes Epilepsy, progressive myoclonic 4, with or without renal failure MIM#254900 for gene: SCARB2
BabyScreen+ newborn screening v1.114 SARS Tommy Li Added phenotypes Neurodevelopmental disorder with microcephaly, ataxia, and seizures MIM#617709 for gene: SARS
BabyScreen+ newborn screening v1.114 SACS Tommy Li Added phenotypes Spastic ataxia, Charlevoix-Saguenay type MIM#270550 for gene: SACS
BabyScreen+ newborn screening v1.114 RUNX2 Tommy Li Added phenotypes Cleidocranial dysplasia MIM#119600; Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600; Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510 for gene: RUNX2
BabyScreen+ newborn screening v1.114 RSPH9 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 12 (MIM#612650) for gene: RSPH9
BabyScreen+ newborn screening v1.114 RSPH4A Tommy Li Added phenotypes Ciliary dyskinesia, primary, 11 (MIM#612649) for gene: RSPH4A
BabyScreen+ newborn screening v1.114 RETREG1 Tommy Li Added phenotypes Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115 for gene: RETREG1
Publications for gene RETREG1 were updated from 31737055; 31596031; 24327336; 19838196 to 19838196; 31737055; 31596031; 24327336
BabyScreen+ newborn screening v1.114 REN Tommy Li Added phenotypes Renal tubular dysgenesis, MIM# 267430 for gene: REN
BabyScreen+ newborn screening v1.114 RASA1 Tommy Li Added phenotypes Capillary malformation-arteriovenous malformation 1, MIM#608354 for gene: RASA1
BabyScreen+ newborn screening v1.114 RAD51B Tommy Li Added phenotypes Breast and/or ovarian cancer for gene: RAD51B
BabyScreen+ newborn screening v1.114 RAB7A Tommy Li Added phenotypes Charcot-Marie-Tooth disease, type 2B, MIM# 600882 for gene: RAB7A
BabyScreen+ newborn screening v1.114 RAB3GAP2 Tommy Li Added phenotypes Warburg micro syndrome 2, MIM# 614225 for gene: RAB3GAP2
BabyScreen+ newborn screening v1.114 RAB3GAP1 Tommy Li Added phenotypes Warburg micro syndrome 1, MIM# 600118 Martsolf syndrome 2, MIM# 619420 for gene: RAB3GAP1
BabyScreen+ newborn screening v1.114 RAB23 Tommy Li Added phenotypes Carpenter syndrome (MIM#201000) for gene: RAB23
BabyScreen+ newborn screening v1.114 RAB10 Tommy Li Added phenotypes Congenital heart disease for gene: RAB10
BabyScreen+ newborn screening v1.114 PYGM Tommy Li Added phenotypes Glycogen storage disease, autosomal dominant; McArdle disease, MIM# 232600 for gene: PYGM
BabyScreen+ newborn screening v1.114 PTH1R Tommy Li Added phenotypes Chondrodysplasia, Blomstrand type MIM#215045; Failure of tooth eruption, primary MIM#125350; Eiken syndrome MIM#600002; Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400 for gene: PTH1R
BabyScreen+ newborn screening v1.114 PSAP Tommy Li Added phenotypes Parkinson disease; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900; Gaucher disease, atypical, MIM# 610539; Krabbe disease, atypical, MIM# 611722; Combined SAP deficiency, MIM# 611721 for gene: PSAP
BabyScreen+ newborn screening v1.114 PRX Tommy Li Added phenotypes Charcot-Marie-Tooth disease, type 4F, MIM# 614895; Dejerine-Sottas disease, MIM# 145900 for gene: PRX
BabyScreen+ newborn screening v1.114 PRPS1 Tommy Li Added phenotypes Arts syndrome; Charcot-Marie-Tooth disease for gene: PRPS1
BabyScreen+ newborn screening v1.114 PRKAG2 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic; Glycogen storage disease of heart, lethal congenital; Wolff-Parkinson-White syndrome for gene: PRKAG2
BabyScreen+ newborn screening v1.114 PRDM16 Tommy Li Added phenotypes Left ventricular noncompaction for gene: PRDM16
BabyScreen+ newborn screening v1.114 POMT2 Tommy Li Added phenotypes Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 MIM# 613158; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156 for gene: POMT2
BabyScreen+ newborn screening v1.114 POMT1 Tommy Li Added phenotypes Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308 for gene: POMT1
BabyScreen+ newborn screening v1.114 POMGNT1 Tommy Li Added phenotypes Retinitis pigmentosa 76, MIM# 617123; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135 for gene: POMGNT1
BabyScreen+ newborn screening v1.114 POLH Tommy Li Added phenotypes Xeroderma pigmentosum, variant type, MIM# 278750 for gene: POLH
BabyScreen+ newborn screening v1.114 PNKD Tommy Li Added phenotypes Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800 for gene: PNKD
BabyScreen+ newborn screening v1.114 PMP22 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, type 1E, MIM# 118300; Roussy-Levy syndrome 180800; Neuropathy, recurrent, with pressure palsies 162500; Dejerine-Sottas disease, MIM# 145900; Charcot-Marie-Tooth disease, type 1A, MIM# 118220 for gene: PMP22
BabyScreen+ newborn screening v1.114 PLP1 Tommy Li Added phenotypes Spastic paraplegia 2, X-linked MIM#312920; Pelizaeus-Merzbacher disease MIM#312080 for gene: PLP1
BabyScreen+ newborn screening v1.114 PLN Tommy Li Added phenotypes Cardiomyopathy, familial hypertrophic; Cardiomyopathy, dilated for gene: PLN
BabyScreen+ newborn screening v1.114 PLEC Tommy Li Added phenotypes Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670 for gene: PLEC
BabyScreen+ newborn screening v1.114 PLA2G6 Tommy Li Added phenotypes Neurodegeneration with brain iron accumulation 2B MIM#610217; Infantile neuroaxonal dystrophy 1 MIM#256600; Parkinson disease 14, autosomal recessive MIM#612953 for gene: PLA2G6
BabyScreen+ newborn screening v1.114 PINK1 Tommy Li Added phenotypes Parkinson disease 6, early onset, MIM#605909 for gene: PINK1
BabyScreen+ newborn screening v1.114 PIEZO2 Tommy Li Added phenotypes Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146; Arthrogryposis, distal, type 5 (MIM#108145); Arthrogryposis, distal, type 3 (MIM#114300); Marden-Walker syndrome (MIM#248700) for gene: PIEZO2
BabyScreen+ newborn screening v1.114 PHOX2A Tommy Li Added phenotypes Fibrosis of extraocular muscles, congenital for gene: PHOX2A
BabyScreen+ newborn screening v1.114 PDSS2 Tommy Li Added phenotypes Leigh syndrome with nephropathy and COQ10 deficiency; Coenzyme Q10 deficiency, primary, 3, MIM# 614652 for gene: PDSS2
BabyScreen+ newborn screening v1.114 PDSS1 Tommy Li Added phenotypes Coenzyme Q10 deficiency, primary, 2, MIM# 614651; Deafness - encephaloneuropathy - obesity - valvulopathy Neonatal for gene: PDSS1
BabyScreen+ newborn screening v1.114 PDLIM3 Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: PDLIM3
BabyScreen+ newborn screening v1.114 PCNT Tommy Li Added phenotypes Microcephalic osteodysplastic primordial dwarfism, type II, 210720 for gene: PCNT
BabyScreen+ newborn screening v1.114 PAK3 Tommy Li Added phenotypes Mental retardation syndrome, X-linked 30, MIM#300558 for gene: PAK3
BabyScreen+ newborn screening v1.114 PABPN1 Tommy Li Added phenotypes Oculopharyngeal muscular dystrophy for gene: PABPN1
BabyScreen+ newborn screening v1.114 P2RX2 Tommy Li Added phenotypes Hearing loss for gene: P2RX2
BabyScreen+ newborn screening v1.114 OSMR Tommy Li Added phenotypes Amyloidosis, primary localized cutaneous, 1 - MIM#105250 for gene: OSMR
BabyScreen+ newborn screening v1.114 OPA3 Tommy Li Added phenotypes 3-methylglutaconic aciduria, type III; Optic atrophy 3 with cataract for gene: OPA3
BabyScreen+ newborn screening v1.114 OPA1 Tommy Li Added phenotypes Optic atrophy 1, MIM#165500; Optic atrophy plus syndrome, MIM# 125250; Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)MIM# 616896; Behr syndrome MIM#210000, AR for gene: OPA1
BabyScreen+ newborn screening v1.114 NUB1 Tommy Li Added phenotypes Congenital heart disease for gene: NUB1
BabyScreen+ newborn screening v1.114 NOTCH3 Tommy Li Added phenotypes Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM# 125310 for gene: NOTCH3
BabyScreen+ newborn screening v1.114 NOG Tommy Li Added phenotypes Multiple synostoses syndrome 1 (MIM#186500); Symphalangism, proximal, 1A (MIM#185800); Brachydactyly, type B2 - MIM#611377; Tarsal-carpal coalition syndrome (MIM#186570); Stapes ankylosis with broad thumbs and toes (MIM#184460) for gene: NOG
BabyScreen+ newborn screening v1.114 NME8 Tommy Li Added phenotypes Ciliary dyskinesia, primary for gene: NME8
BabyScreen+ newborn screening v1.114 NFATC1 Tommy Li Added phenotypes Congenital heart disease for gene: NFATC1
BabyScreen+ newborn screening v1.114 NEXN Tommy Li Added phenotypes Cardiomyopathy, familial hypertrophic; Cardiomyopathy, dilated for gene: NEXN
BabyScreen+ newborn screening v1.114 NEFL Tommy Li Added phenotypes Charcot-Marie-Tooth disease, dominant intermediate G, MIM# 617882; Charcot-Marie-Tooth disease, type 2E 607684; Charcot-Marie-Tooth disease, type 1F, MIM# 607734 for gene: NEFL
BabyScreen+ newborn screening v1.114 NEBL Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: NEBL
BabyScreen+ newborn screening v1.114 NEB Tommy Li Added phenotypes Arthrogryposis multiplex congenita 6, MIM# 619334; Nemaline myopathy 2, autosomal recessive 256030 for gene: NEB
BabyScreen+ newborn screening v1.114 NAXE Tommy Li Added phenotypes Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186 for gene: NAXE
Publications for gene NAXE were updated from 27122014; 27616477; 31758406 to 27616477; 27122014; 31758406
BabyScreen+ newborn screening v1.114 NAA15 Tommy Li Added phenotypes Congenital heart disease for gene: NAA15
BabyScreen+ newborn screening v1.114 MYPN Tommy Li Added phenotypes Cardiomyopathy, hypertrophic; Cardiomyopathy, dilated for gene: MYPN
BabyScreen+ newborn screening v1.114 MYOZ2 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic for gene: MYOZ2
BabyScreen+ newborn screening v1.114 MYOT Tommy Li Added phenotypes Myofibrillar myopathy for gene: MYOT
BabyScreen+ newborn screening v1.114 MYOM1 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic for gene: MYOM1
BabyScreen+ newborn screening v1.114 MYO1F Tommy Li Added phenotypes Sensorineural hearing loss for gene: MYO1F
BabyScreen+ newborn screening v1.114 MYO1C Tommy Li Added phenotypes Sensorineural hearing loss for gene: MYO1C
BabyScreen+ newborn screening v1.114 MYLK2 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic for gene: MYLK2
BabyScreen+ newborn screening v1.114 MYH9 Tommy Li Added phenotypes Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100; Deafness, autosomal dominant 17, MIM# 603622 for gene: MYH9
BabyScreen+ newborn screening v1.114 MYH6 Tommy Li Added phenotypes Atrial septal defect; Cardiomyopathy, familial hypertrophic; Cardiomyopathy, dilated for gene: MYH6
BabyScreen+ newborn screening v1.114 MYH3 Tommy Li Added phenotypes Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436 for gene: MYH3
BabyScreen+ newborn screening v1.114 MYH14 Tommy Li Added phenotypes Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369; Deafness, autosomal dominant 4A, MIM# 600652 for gene: MYH14
BabyScreen+ newborn screening v1.114 MYBPC3 Tommy Li Added phenotypes Cardiomyopathy, familial hypertrophic; Cardiomyopathy, dilated for gene: MYBPC3
BabyScreen+ newborn screening v1.114 MYBPC1 Tommy Li Added phenotypes Myopathy, congenital, with tremor MIM#618524; Lethal congenital contracture syndrome 4, MIM# 614915; Arthrogryposis, distal, type 1B 614335 for gene: MYBPC1
Publications for gene MYBPC1 were updated from 23873045; 20045868; 22610851; 26661508; 31025394; 31264822 to 20045868; 23873045; 31025394; 31264822; 26661508; 22610851
BabyScreen+ newborn screening v1.114 MUC5B Tommy Li Added phenotypes Pulmonary fibrosis, idiopathic for gene: MUC5B
BabyScreen+ newborn screening v1.114 MTO1 Tommy Li Added phenotypes Hypertrophic cardiomyopathy & lactic acidosis for gene: MTO1
BabyScreen+ newborn screening v1.114 MT-ND6 Tommy Li Added phenotypes Leber hereditary optic neuropathy for gene: MT-ND6
BabyScreen+ newborn screening v1.114 MT-ND4 Tommy Li Added phenotypes Leber hereditary optic neuropathy for gene: MT-ND4
BabyScreen+ newborn screening v1.114 MT-ND1 Tommy Li Added phenotypes Leber hereditary optic neuropathy for gene: MT-ND1
BabyScreen+ newborn screening v1.114 MTM1 Tommy Li Added phenotypes Myopathy, centronuclear, X-linked, MIM# 310400 for gene: MTM1
BabyScreen+ newborn screening v1.114 MSX2 Tommy Li Added phenotypes Craniosynostosis 2 (MIM#604757); Parietal foramina 1 (MIM#168500); Parietal foramina with cleidocranial dysplasia (MIM#168550) for gene: MSX2
BabyScreen+ newborn screening v1.114 MPZ Tommy Li Added phenotypes Charcot Marie Tooth disease, type 2I, 607677; Charcot Marie Tooth disease, type 1B, 118200; Dejerine Sottas disease, 145900; Neuropathy, congenital hypomyelinating, 605253; Charcot Marie Tooth disease, type 2J, 607736; Charcot Marie Tooth disease, dominant intermediate D, 60779 for gene: MPZ
BabyScreen+ newborn screening v1.114 MKS1 Tommy Li Added phenotypes Meckel syndrome 1, MIM# 249000 MONDO:0009571; Bardet-Biedl syndrome 13, MIM# 615990 MONDO:0014441; Joubert syndrome 28, MIM# 617121 MONDO:0014928 for gene: MKS1
BabyScreen+ newborn screening v1.114 MKKS Tommy Li Added phenotypes Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700 for gene: MKKS
BabyScreen+ newborn screening v1.114 MIR96 Tommy Li Added phenotypes Hearing loss for gene: MIR96
BabyScreen+ newborn screening v1.114 MIB1 Tommy Li Added phenotypes Left ventricular noncompaction for gene: MIB1
BabyScreen+ newborn screening v1.114 MFN2 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260; Hereditary motor and sensory neuropathy VIA, OMIM #601152; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087 for gene: MFN2
BabyScreen+ newborn screening v1.114 MEGF10 Tommy Li Added phenotypes Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399 for gene: MEGF10
BabyScreen+ newborn screening v1.114 MED25 Tommy Li Added phenotypes Congenital cataract-microcephaly-naevus flammeus syndrome MONDO:0014643; Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449 for gene: MED25
BabyScreen+ newborn screening v1.114 MED20 Tommy Li Added phenotypes Congenital heart disease for gene: MED20
BabyScreen+ newborn screening v1.114 MED13L Tommy Li Added phenotypes Transposition of great arteries for gene: MED13L
BabyScreen+ newborn screening v1.114 MED12 Tommy Li Added phenotypes Opitz-Kaveggia syndrome MIM#305450; Lujan-Fryns syndrome MIM#309520; Hardikar syndrome, MIM# 301068; Ohdo syndrome, X-linked MIM#300895 for gene: MED12
BabyScreen+ newborn screening v1.114 MECP2 Tommy Li Added phenotypes MECP2-related disorders Rett syndrome, MIM# 312750 Mental retardation, X-linked, syndromic 13, MIM# 300055 for gene: MECP2
BabyScreen+ newborn screening v1.114 MCPH1 Tommy Li Added phenotypes Microcephaly 1, primary, autosomal recessive, MIM# 251200 for gene: MCPH1
BabyScreen+ newborn screening v1.114 MCCC2 Tommy Li Added phenotypes 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210 for gene: MCCC2
BabyScreen+ newborn screening v1.114 MCCC1 Tommy Li Added phenotypes 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200 for gene: MCCC1
BabyScreen+ newborn screening v1.114 MAPT Tommy Li Added phenotypes Dementia, frontotemporal, with or without parkinsonism for gene: MAPT
BabyScreen+ newborn screening v1.114 MAP2K2 Tommy Li Added phenotypes Cardiofaciocutaneous syndrome 4, MIM# 615280 for gene: MAP2K2
BabyScreen+ newborn screening v1.114 MAP2K1 Tommy Li Added phenotypes Cardiofaciocutaneous syndrome 3, MIM# 615279 for gene: MAP2K1
BabyScreen+ newborn screening v1.114 LRSAM1 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, axonal, type 2P, MIM# 614436 for gene: LRSAM1
BabyScreen+ newborn screening v1.114 LRRK2 Tommy Li Added phenotypes Parkinson disease for gene: LRRK2
BabyScreen+ newborn screening v1.114 LRRC6 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 19, MIM# 614935 for gene: LRRC6
BabyScreen+ newborn screening v1.114 LRPPRC Tommy Li Added phenotypes Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111 for gene: LRPPRC
BabyScreen+ newborn screening v1.114 LRP2 Tommy Li Added phenotypes Donnai-Barrow syndrome, MIM#222448 for gene: LRP2
BabyScreen+ newborn screening v1.114 LMNB2 Tommy Li Added phenotypes Lipodystrophy, partial for gene: LMNB2
BabyScreen+ newborn screening v1.114 LITAF Tommy Li Added phenotypes Charcot-Marie-Tooth disease, type 1C, MIM# 601098 for gene: LITAF
BabyScreen+ newborn screening v1.114 LIFR Tommy Li Added phenotypes Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, MIM# 601559 for gene: LIFR
BabyScreen+ newborn screening v1.114 LDB3 Tommy Li Added phenotypes Myofibrillar myopathy for gene: LDB3
BabyScreen+ newborn screening v1.114 LARS2 Tommy Li Added phenotypes Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Perrault syndrome 4, MIM# 615300 for gene: LARS2
BabyScreen+ newborn screening v1.114 LARS Tommy Li Added phenotypes Infantile liver failure syndrome for gene: LARS
BabyScreen+ newborn screening v1.114 LARGE1 Tommy Li Added phenotypes Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154 for gene: LARGE1
BabyScreen+ newborn screening v1.114 LAMB2 Tommy Li Added phenotypes Pierson syndrome, MIM# 609049; Nephrotic syndrome, type 5, with or without ocular abnormalities, MIM# 614199 for gene: LAMB2
BabyScreen+ newborn screening v1.114 LAMA4 Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: LAMA4
BabyScreen+ newborn screening v1.114 KRT5 Tommy Li Added phenotypes Epidermolysis bullosa simplex, recessive 1, MIM# 601001; Dowling-Degos disease 1, MIM# 179850; Epidermolysis bullosa simplex-MP 131960; Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800; Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760; Epidermolysis bullosa simplex, Koebner type, MIM# 131900; Epidermolysis bullosa simplex-MCR, MIM# 609352 for gene: KRT5
BabyScreen+ newborn screening v1.114 KRT16 Tommy Li Added phenotypes Palmoplantar keratoderma, nonepidermolytic, focal (MIM#613000) Pachyonychia congenita 1 (MIM#167200) for gene: KRT16
BabyScreen+ newborn screening v1.114 KRT14 Tommy Li Added phenotypes Epidermolysis bullosa simplex, recessive 1, 601001; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000; Epidermolysis bullosa simplex, Koebner type, 131900; Dermatopathia pigmentosa reticularis, 125595 for gene: KRT14
BabyScreen+ newborn screening v1.114 KRAS Tommy Li Added phenotypes Noonan syndrome 3, MIM# 609942; Cardiofaciocutaneous syndrome 2, MIM# 615278 for gene: KRAS
BabyScreen+ newborn screening v1.114 KIF21A Tommy Li Added phenotypes Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700 for gene: KIF21A
BabyScreen+ newborn screening v1.114 KIF1B Tommy Li Added phenotypes Charcot-Marie-Tooth disease for gene: KIF1B
BabyScreen+ newborn screening v1.114 KDM5B Tommy Li Added phenotypes Congenital heart disease for gene: KDM5B
BabyScreen+ newborn screening v1.114 KCTD7 Tommy Li Added phenotypes Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726) for gene: KCTD7
BabyScreen+ newborn screening v1.114 KCNJ18 Tommy Li Added phenotypes Hypokalaemic periodic paralysis for gene: KCNJ18
BabyScreen+ newborn screening v1.114 KBTBD13 Tommy Li Added phenotypes Nemaline myopathy 6, autosomal dominant, MIM# 609273; Hereditary motor neuropathy late-onset; limb girdle muscular dystrophy for gene: KBTBD13
BabyScreen+ newborn screening v1.114 KAT6B Tommy Li Added phenotypes SBBYSS syndrome MIM #603736; Genitopatellar syndrome MIM #606170 for gene: KAT6B
BabyScreen+ newborn screening v1.114 KARS Tommy Li Added phenotypes Deafness, autosomal recessive 89, MIM# 613916; Leukoencephalopathy with or without deafness (LEPID), MIM#619147; Congenital deafness and adult-onset progressive leukoencephalopathy (DEAPLE), MIM#619196 for gene: KARS
Publications for gene KARS were updated from 30737337; 30715177; 31116475 to 30737337; 31116475; 30715177
BabyScreen+ newborn screening v1.114 JPH2 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic for gene: JPH2
BabyScreen+ newborn screening v1.114 ITGA7 Tommy Li Added phenotypes Congenital muscular dystrophy with integrin deficiency for gene: ITGA7
BabyScreen+ newborn screening v1.114 ISPD Tommy Li Added phenotypes Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643 Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052 for gene: ISPD
BabyScreen+ newborn screening v1.114 ILK Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: ILK
BabyScreen+ newborn screening v1.114 IGHMBP2 Tommy Li Added phenotypes Neuronopathy, distal hereditary motor, type VI, MIM# 604320; Charcot-Marie-Tooth disease, axonal, type 2S, MIM# 616155 for gene: IGHMBP2
BabyScreen+ newborn screening v1.114 HYDIN Tommy Li Added phenotypes Primary ciliary dyskinesia for gene: HYDIN
BabyScreen+ newborn screening v1.114 HTRA1 Tommy Li Added phenotypes CARASIL syndrome, MIM# 600142 for gene: HTRA1
BabyScreen+ newborn screening v1.114 HSPG2 Tommy Li Added phenotypes Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; Schwartz-Jampel syndrome, type 1, MIM# 255800; MONDO:0009717; MONDO:0009140 for gene: HSPG2
BabyScreen+ newborn screening v1.114 HSPB8 Tommy Li Added phenotypes Neuropathy, distal hereditary motor type IIA, 158590; Charcot-Marie-Tooth disease, axonal, type 2L, MIM# 608673 for gene: HSPB8
BabyScreen+ newborn screening v1.114 HSD17B4 Tommy Li Added phenotypes Perrault syndrome 1, AR (MIM#233400); D-bifunctional protein deficiency, AR (MIM#261515) for gene: HSD17B4
BabyScreen+ newborn screening v1.114 HOMEZ Tommy Li Added phenotypes Congenital heart disease for gene: HOMEZ
BabyScreen+ newborn screening v1.114 HINT1 Tommy Li Added phenotypes Gamstorp-Wohlfart syndrome, MONDO:0007646; Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200 for gene: HINT1
BabyScreen+ newborn screening v1.114 HGSNAT Tommy Li Added phenotypes Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930 for gene: HGSNAT
BabyScreen+ newborn screening v1.114 HAS2 Tommy Li Added phenotypes Congenital heart disease for gene: HAS2
BabyScreen+ newborn screening v1.114 HARS2 Tommy Li Added phenotypes Perrault syndrome 2, MIM# 614926 for gene: HARS2
BabyScreen+ newborn screening v1.114 HARS Tommy Li Added phenotypes Usher syndrome type 3B for gene: HARS
BabyScreen+ newborn screening v1.114 GPR143 Tommy Li Added phenotypes Ocular albinism, type I, Nettleship-Falls type, MIM# 300500 for gene: GPR143
BabyScreen+ newborn screening v1.114 GNS Tommy Li Added phenotypes Mucopolysaccharidosis type IIID, MIM# 252940 for gene: GNS
BabyScreen+ newborn screening v1.114 GLE1 Tommy Li Added phenotypes Lethal arthrogryposis with anterior horn cell disease for gene: GLE1
BabyScreen+ newborn screening v1.114 GLB1 Tommy Li Added phenotypes GM1-gangliosidosis, type I MIM#230500; Mucopolysaccharidosis type IVB (Morquio) MIM#253010; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650 for gene: GLB1
BabyScreen+ newborn screening v1.114 GJC2 Tommy Li Added phenotypes Lymphatic malformation 3 MIM#613480; Spastic paraplegia 44, autosomal recessive MIM#613206; Leukodystrophy, hypomyelinating, 2 MIM#608804 for gene: GJC2
BabyScreen+ newborn screening v1.114 GJB1 Tommy Li Added phenotypes Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800 for gene: GJB1
BabyScreen+ newborn screening v1.114 GFER Tommy Li Added phenotypes Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay for gene: GFER
BabyScreen+ newborn screening v1.114 GDF1 Tommy Li Added phenotypes Congenital heart defects for gene: GDF1
BabyScreen+ newborn screening v1.114 GDAP1 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, recessive intermediate, A, MIM#608340; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM#607706; Charcot-Marie-Tooth disease, type 4A, MIM#214400; Charcot-Marie-Tooth disease, axonal, type 2K, MIM#607831 for gene: GDAP1
BabyScreen+ newborn screening v1.114 GATAD1 Tommy Li Added phenotypes Cardiomyopathy, dilated, 2B for gene: GATAD1
BabyScreen+ newborn screening v1.114 GABRG2 Tommy Li Added phenotypes Epileptic encephalopathy, early infantile, 74 MIM# 618396; Febrile seizures, familial, 8 MIM# 607681; Epilepsy, generalized, with febrile seizures plus, type 3 MIM# 607681 for gene: GABRG2
BabyScreen+ newborn screening v1.114 FOXI1 Tommy Li Added phenotypes autosomal recessive distal renal tubular acidosis MONDO:0018440 for gene: FOXI1
BabyScreen+ newborn screening v1.114 FOXH1 Tommy Li Added phenotypes Congenital heart defects for gene: FOXH1
BabyScreen+ newborn screening v1.114 FOXF1 Tommy Li Added phenotypes Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380 for gene: FOXF1
BabyScreen+ newborn screening v1.114 FLNC Tommy Li Added phenotypes Myofibrillar myopathy for gene: FLNC
BabyScreen+ newborn screening v1.114 FLG Tommy Li Added phenotypes Ichthyosis vulgaris for gene: FLG
BabyScreen+ newborn screening v1.114 FKTN Tommy Li Added phenotypes Muscular dystrophy-dystroglycanopathy MONDO:0018276 for gene: FKTN
BabyScreen+ newborn screening v1.114 FKRP Tommy Li Added phenotypes Muscular dystrophy-dystroglycanopathy MONDO:0018276 for gene: FKRP
BabyScreen+ newborn screening v1.114 FHL2 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic for gene: FHL2
BabyScreen+ newborn screening v1.114 FHL1 Tommy Li Added phenotypes Emery-Dreifuss muscular dystrophy; Myofibrillar myopathy for gene: FHL1
BabyScreen+ newborn screening v1.114 FGFR2 Tommy Li Added phenotypes Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410; Crouzon syndrome , MIM#123500; Beare-Stevenson cutis gyrata syndrome, MIM# 123790; Apert syndrome, MIM# 101200; LADD syndrome, MIM# 149730; Bent bone dysplasia syndrome, MIM# 614592; Jackson-Weiss syndrome,MIM# 123150; Pfeiffer syndrome,MIM# 101600; Saethre-Chotzen syndrome 101400; Craniofacial-skeletal-dermatologic dysplasia, MIM# 101600 for gene: FGFR2
BabyScreen+ newborn screening v1.114 FGFR1 Tommy Li Added phenotypes Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Jackson-Weiss syndrome 123150; Osteoglophonic dysplasia 166250; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Pfeiffer syndrome 101600; Trigonocephaly 1 190440 for gene: FGFR1
BabyScreen+ newborn screening v1.114 FGD4 Tommy Li Added phenotypes Charcot Marie Tooth disease, type 4H, MIM#609311 for gene: FGD4
BabyScreen+ newborn screening v1.114 FGD1 Tommy Li Added phenotypes Mental retardation, X-linked syndromic 16, MIM# 305400; Aarskog-Scott syndrome, MIM # 305400 for gene: FGD1
BabyScreen+ newborn screening v1.114 FBN2 Tommy Li Added phenotypes Contractural arachnodactyly, congenital MIM#121050 for gene: FBN2
BabyScreen+ newborn screening v1.114 FBLN5 Tommy Li Added phenotypes Age-related macular degeneration; Cutis laxa for gene: FBLN5
BabyScreen+ newborn screening v1.114 FAM111B Tommy Li Added phenotypes Hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis for gene: FAM111B
BabyScreen+ newborn screening v1.114 EYA1 Tommy Li Added phenotypes Branchiootorenal syndrome 1, with or without cataracts MIM#113650; Anterior segment anomalies with or without cataract MIM#602588; Branchiootic syndrome 1 MIM#602588 for gene: EYA1
BabyScreen+ newborn screening v1.114 ESCO2 Tommy Li Added phenotypes Juberg-Hayward syndrome, MIM# 216100; Roberts-SC phocomelia syndrome, MIM#268300 for gene: ESCO2
BabyScreen+ newborn screening v1.114 EMD Tommy Li Added phenotypes Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300 for gene: EMD
BabyScreen+ newborn screening v1.114 ELN Tommy Li Added phenotypes supravalvular aortic stenosis MONDO:0008504; cutis laxa, autosomal dominant 1 MONDO:0007411 for gene: ELN
BabyScreen+ newborn screening v1.114 EGR2 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, type 1D 607678; Dejerine-Sottas disease 145900; Hypomyelinating neuropathy, congenital, 1, MIM# 605253 for gene: EGR2
BabyScreen+ newborn screening v1.114 EDARADD Tommy Li Added phenotypes autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619 for gene: EDARADD
BabyScreen+ newborn screening v1.114 EDAR Tommy Li Added phenotypes autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619 for gene: EDAR
BabyScreen+ newborn screening v1.114 DYSF Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768; Miyoshi muscular dystrophy 1 254130 for gene: DYSF
BabyScreen+ newborn screening v1.114 DTNA Tommy Li Added phenotypes Left ventricular noncompaction 1 for gene: DTNA
BabyScreen+ newborn screening v1.114 DPP6 Tommy Li Added phenotypes Ventricular fibrillation, paroxysmal familial, 2 for gene: DPP6
BabyScreen+ newborn screening v1.114 DNM2 Tommy Li Added phenotypes Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482 Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482 for gene: DNM2
BabyScreen+ newborn screening v1.114 DNAL1 Tommy Li Added phenotypes Primary ciliary dyskinesia for gene: DNAL1
BabyScreen+ newborn screening v1.114 DNAJB6 Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal dominant 1 MIM#603511 for gene: DNAJB6
BabyScreen+ newborn screening v1.114 DNAI2 Tommy Li Added phenotypes Primary ciliary dyskinesia for gene: DNAI2
BabyScreen+ newborn screening v1.114 DNAI1 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400 for gene: DNAI1
BabyScreen+ newborn screening v1.114 DNAH5 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644 for gene: DNAH5
BabyScreen+ newborn screening v1.114 DNAH11 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884 for gene: DNAH11
BabyScreen+ newborn screening v1.114 DNAAF5 Tommy Li Added phenotypes Primary ciliary dyskinesia for gene: DNAAF5
BabyScreen+ newborn screening v1.114 DNAAF3 Tommy Li Added phenotypes Primary ciliary dyskinesia for gene: DNAAF3
BabyScreen+ newborn screening v1.114 DNAAF2 Tommy Li Added phenotypes Primary ciliary dyskinesia for gene: DNAAF2
BabyScreen+ newborn screening v1.114 DNAAF1 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 13, MIM# 613193 for gene: DNAAF1
BabyScreen+ newborn screening v1.114 DLC1 Tommy Li Added phenotypes Congenital heart disease for gene: DLC1
BabyScreen+ newborn screening v1.114 DDR2 Tommy Li Added phenotypes Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665; Warburg-Cinotti syndrome, MIM# 618175 for gene: DDR2
BabyScreen+ newborn screening v1.114 DDHD1 Tommy Li Added phenotypes Spastic paraplegia for gene: DDHD1
BabyScreen+ newborn screening v1.114 DAPK3 Tommy Li Added phenotypes Congenital heart disease for gene: DAPK3
BabyScreen+ newborn screening v1.114 DAG1 Tommy Li Added phenotypes Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9 for gene: DAG1
BabyScreen+ newborn screening v1.114 D2HGDH Tommy Li Added phenotypes D-2-hydroxyglutaric aciduria MIM#600721 for gene: D2HGDH
BabyScreen+ newborn screening v1.114 CTF1 Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: CTF1
BabyScreen+ newborn screening v1.114 CTDP1 Tommy Li Added phenotypes Congenital cataracts - facial dysmorphism - neuropathy for gene: CTDP1
BabyScreen+ newborn screening v1.114 CSRP3 Tommy Li Added phenotypes Cardiomyopathy, familial hypertrophic, 12; Cardiomyopathy, dilated, 1M for gene: CSRP3
BabyScreen+ newborn screening v1.114 CSF2RB Tommy Li Added phenotypes Pulmonary alveolar proteinosis for gene: CSF2RB
BabyScreen+ newborn screening v1.114 CSF2RA Tommy Li Added phenotypes Surfactant metabolism dysfunction, pulmonary, 4, MIM# 300770 for gene: CSF2RA
Publications for gene CSF2RA were updated from 25425184; 18955570; 20622029 to 18955570; 25425184; 20622029
BabyScreen+ newborn screening v1.114 CSF1R Tommy Li Added phenotypes Leukoencephalopathy, diffuse hereditary, with spheroids for gene: CSF1R
BabyScreen+ newborn screening v1.114 CRELD1 Tommy Li Added phenotypes Cardiac atrioventricular septal defect for gene: CRELD1
BabyScreen+ newborn screening v1.114 CR2 Tommy Li Added phenotypes Immunodeficiency, common variable, 7, MIM# 614699 for gene: CR2
BabyScreen+ newborn screening v1.114 COX4I2 Tommy Li Added phenotypes Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis for gene: COX4I2
BabyScreen+ newborn screening v1.114 COQ9 Tommy Li Added phenotypes Coenzyme Q10 deficiency, primary, 5 , MIM#614654 for gene: COQ9
BabyScreen+ newborn screening v1.114 COL7A1 Tommy Li Added phenotypes EBD inversa, MIM# 226600; Epidermolysis bullosa, pretibial, MIM# 131850; EBD, Bart type MIM# 132000 EBD, localisata variant; Epidermolysis bullosa pruriginosa 604129; Epidermolysis bullosa dystrophica, MIM# 131750; Epidermolysis bullosa dystrophica, 226600; Transient bullous of the newborn 131705 for gene: COL7A1
BabyScreen+ newborn screening v1.114 COL6A3 Tommy Li Added phenotypes Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090; Dystonia 27 MIM#616411 for gene: COL6A3
BabyScreen+ newborn screening v1.114 COL6A2 Tommy Li Added phenotypes Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090 for gene: COL6A2
BabyScreen+ newborn screening v1.114 COL6A1 Tommy Li Added phenotypes Bethlem myopathy MIM#158810; Ullrich congenital muscular dystrophy MIM#254090 for gene: COL6A1
BabyScreen+ newborn screening v1.114 COL5A1 Tommy Li Added phenotypes Fibromuscular dysplasia, multifocal, MIM# 619329; Ehlers-Danlos syndrome, classic type, 1, MIM# 130000 for gene: COL5A1
BabyScreen+ newborn screening v1.114 CLN8 Tommy Li Added phenotypes Ceroid lipofuscinosis, neuronal, 8, MIM# 600143; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003 for gene: CLN8
BabyScreen+ newborn screening v1.114 CITED2 Tommy Li Added phenotypes Congenital heart defects for gene: CITED2
BabyScreen+ newborn screening v1.114 CHST3 Tommy Li Added phenotypes Larsen syndrome for gene: CHST3
BabyScreen+ newborn screening v1.114 CHRNG Tommy Li Added phenotypes Multiple pterygium syndrome, lethal type, MIM# 253290; Escobar syndrome, MIM# 265000 for gene: CHRNG
BabyScreen+ newborn screening v1.114 CHRM2 Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: CHRM2
BabyScreen+ newborn screening v1.114 CHKB Tommy Li Added phenotypes Muscular dystrophy, congenital, megaconial type, MIM# 602541 for gene: CHKB
BabyScreen+ newborn screening v1.114 CHD7 Tommy Li Added phenotypes CHARGE syndrome, MIM# 214800 for gene: CHD7
BabyScreen+ newborn screening v1.114 CEP78 Tommy Li Added phenotypes Cone-rod dystrophy and hearing loss MIM#617236 for gene: CEP78
BabyScreen+ newborn screening v1.114 CEP290 Tommy Li Added phenotypes Senior-Loken syndrome 6, MIM# 610189; Meckel syndrome 4, MIM# 611134; Joubert syndrome 5 610188; Leber congenital amaurosis 10, MIM# 611755; Bardet-Biedl syndrome 14, MIM# 615991 for gene: CEP290
BabyScreen+ newborn screening v1.114 CEP250 Tommy Li Added phenotypes Cone-rod dystrophy and hearing loss 2 MIM#618358 for gene: CEP250
BabyScreen+ newborn screening v1.114 CEP152 Tommy Li Added phenotypes Seckel syndrome 5, MIM# 613823; Microcephaly 9, primary, autosomal recessive, MIM# 614852 for gene: CEP152
BabyScreen+ newborn screening v1.114 CENPJ Tommy Li Added phenotypes Primary microcephaly for gene: CENPJ
BabyScreen+ newborn screening v1.114 CEACAM16 Tommy Li Added phenotypes Hearing loss, autosomal dominant for gene: CEACAM16
BabyScreen+ newborn screening v1.114 CDKL5 Tommy Li Added phenotypes Epileptic encephalopathy, early infantile, 2, MIM 300672 for gene: CDKL5
BabyScreen+ newborn screening v1.114 CDK5RAP2 Tommy Li Added phenotypes MONDO:0011488; Microcephaly 3, primary, autosomal recessive, MIM# 604804 for gene: CDK5RAP2
BabyScreen+ newborn screening v1.114 CD81 Tommy Li Added phenotypes Immunodeficiency, common variable, 6, MIM# 613496 for gene: CD81
BabyScreen+ newborn screening v1.114 CCDC40 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 15, MIM#613808 for gene: CCDC40
BabyScreen+ newborn screening v1.114 CCDC39 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 14, MIM# 613807 for gene: CCDC39
BabyScreen+ newborn screening v1.114 CCDC103 Tommy Li Added phenotypes Primary ciliary dyskinesia for gene: CCDC103
BabyScreen+ newborn screening v1.114 CAVIN4 Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: CAVIN4
BabyScreen+ newborn screening v1.114 CASK Tommy Li Added phenotypes FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422 for gene: CASK
BabyScreen+ newborn screening v1.114 CARS2 Tommy Li Added phenotypes Epileptic encephalopathy for gene: CARS2
BabyScreen+ newborn screening v1.114 CAPN3 Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600 for gene: CAPN3
BabyScreen+ newborn screening v1.114 CACNA1F Tommy Li Added phenotypes Night blindness, congenital stationary (incomplete), 2A, X-linked MIM#300071; Cone-rod dystrophy, X-linked, 3 MIM#300476; Aland Island eye disease MIM#300600 for gene: CACNA1F
BabyScreen+ newborn screening v1.114 CACNA1D Tommy Li Added phenotypes Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474; Sinoatrial node dysfunction and deafness for gene: CACNA1D
BabyScreen+ newborn screening v1.114 BVES Tommy Li Added phenotypes Congenital heart disease for gene: BVES
BabyScreen+ newborn screening v1.114 BRAF Tommy Li Added phenotypes Noonan syndrome 7, MIM# 613706; Cardiofaciocutaneous syndrome, MIM# 115150 for gene: BRAF
BabyScreen+ newborn screening v1.114 BNC2 Tommy Li Added phenotypes Total anomalous pulmonary venous return for gene: BNC2
BabyScreen+ newborn screening v1.114 BMPR2 Tommy Li Added phenotypes Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600 for gene: BMPR2
BabyScreen+ newborn screening v1.114 BIN1 Tommy Li Added phenotypes Centronuclear myopathy 2, MIM# 255200 for gene: BIN1
BabyScreen+ newborn screening v1.114 BICD2 Tommy Li Added phenotypes Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291; Neurodevelopmental disorder (MONDO#0700092), BICD2-related for gene: BICD2
Publications for gene BICD2 were updated from 23664116; 23664119; 23664120; 27751653; 28635954; 30054298; 29528393; 35896821 to 23664120; 30054298; 28635954; 29528393; 35896821; 27751653; 23664116; 23664119
BabyScreen+ newborn screening v1.114 BCL9 Tommy Li Added phenotypes Congenital heart disease for gene: BCL9
BabyScreen+ newborn screening v1.114 BBS9 Tommy Li Added phenotypes Bardet-Biedl syndrome 9, MIM#615986 for gene: BBS9
BabyScreen+ newborn screening v1.114 BBS7 Tommy Li Added phenotypes Bardet-Biedl syndrome 7, MIM# 615984 for gene: BBS7
BabyScreen+ newborn screening v1.114 BBS5 Tommy Li Added phenotypes Bardet-Biedl syndrome 5, MIM#615983 for gene: BBS5
BabyScreen+ newborn screening v1.114 BBS4 Tommy Li Added phenotypes Bardet-Biedl syndrome 4, MIM#615982 for gene: BBS4
BabyScreen+ newborn screening v1.114 BBS2 Tommy Li Added phenotypes Bardet-Biedl syndrome 2, MIM# 615981 for gene: BBS2
BabyScreen+ newborn screening v1.114 BBS12 Tommy Li Added phenotypes Bardet-Biedl syndrome 12, MIM# 615989 for gene: BBS12
BabyScreen+ newborn screening v1.114 BBS10 Tommy Li Added phenotypes Bardet-Biedl syndrome 10, MIM# 615987 for gene: BBS10
BabyScreen+ newborn screening v1.114 BBS1 Tommy Li Added phenotypes Bardet-Biedl syndrome 1, MIM# 209900 for gene: BBS1
BabyScreen+ newborn screening v1.114 BARD1 Tommy Li Added phenotypes Tetralogy of Fallot for gene: BARD1
BabyScreen+ newborn screening v1.114 BAG3 Tommy Li Added phenotypes Myopathy, myofibrillar; Cardiomyopathy, dilated for gene: BAG3
BabyScreen+ newborn screening v1.114 B3GAT3 Tommy Li Added phenotypes Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects for gene: B3GAT3
BabyScreen+ newborn screening v1.114 ATP1A3 Tommy Li Added phenotypes Rapid-onset dystonia-parkinsonism for gene: ATP1A3
BabyScreen+ newborn screening v1.114 ARX Tommy Li Added phenotypes Lissencephaly, X-linked 2, MIM# 300215 for gene: ARX
BabyScreen+ newborn screening v1.114 ARSE Tommy Li Added phenotypes Chondrodysplasia punctata, X-linked recessive for gene: ARSE
BabyScreen+ newborn screening v1.114 ARMC4 Tommy Li Added phenotypes Ciliary dyskinesia, primary, 23, MIM# 615451 for gene: ARMC4
BabyScreen+ newborn screening v1.114 ARL13B Tommy Li Added phenotypes Joubert syndrome for gene: ARL13B
BabyScreen+ newborn screening v1.114 ARID1B Tommy Li Added phenotypes Coffin-Siris syndrome 1 MIM#135900 for gene: ARID1B
BabyScreen+ newborn screening v1.114 ARID1A Tommy Li Added phenotypes Coffin-Siris syndrome for gene: ARID1A
BabyScreen+ newborn screening v1.114 ARHGEF9 Tommy Li Added phenotypes Hyperekplexia and epilepsy for gene: ARHGEF9
BabyScreen+ newborn screening v1.114 ARHGAP31 Tommy Li Added phenotypes Syndromic cutis aplasia & limb anomalies for gene: ARHGAP31
BabyScreen+ newborn screening v1.114 ARFGEF2 Tommy Li Added phenotypes Periventricular heterotopia with microcephaly (MIM#608097) for gene: ARFGEF2
BabyScreen+ newborn screening v1.114 AR Tommy Li Added phenotypes Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300 for gene: AR
BabyScreen+ newborn screening v1.114 APTX Tommy Li Added phenotypes Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia MIM#208920 for gene: APTX
Publications for gene APTX were updated from 30986824; 26256098; 11586299 to 26256098; 11586299; 30986824
BabyScreen+ newborn screening v1.114 AP4M1 Tommy Li Added phenotypes Spastic paraplegia 50, autosomal recessive, MIM# 612936 for gene: AP4M1
Publications for gene AP4M1 were updated from 31915823; 32979048; 19559397; 25496299; 21937992; 28464862; 29096665 to 31915823; 25496299; 29096665; 32979048; 21937992; 19559397; 28464862
BabyScreen+ newborn screening v1.114 AP4E1 Tommy Li Added phenotypes Spastic paraplegia 51, autosomal recessive, MIM# 613744 for gene: AP4E1
Publications for gene AP4E1 were updated from 20972249; 32979048; 23472171; 21620353; 21937992 to 20972249; 32979048; 21620353; 21937992; 23472171
BabyScreen+ newborn screening v1.114 AP4B1 Tommy Li Added phenotypes Spastic paraplegia 47, autosomal recessive, MIM# 614066 for gene: AP4B1
Publications for gene AP4B1 were updated from 24700674; 32979048; 32166732; 32171285; 22290197; 21620353; 31525725; 24781758 to 32171285; 24700674; 22290197; 24781758; 32166732; 21620353; 32979048; 31525725
BabyScreen+ newborn screening v1.114 AP1S3 Tommy Li Added phenotypes Pustular psoriasis for gene: AP1S3
BabyScreen+ newborn screening v1.114 ANO5 Tommy Li Added phenotypes Muscular dystrophy, limb-girdle, type 2L; Gnathodiaphyseal dysplasia for gene: ANO5
BabyScreen+ newborn screening v1.114 ANO10 Tommy Li Added phenotypes Spinocerebellar ataxia, autosomal recessive 10, MIM#613728 for gene: ANO10
BabyScreen+ newborn screening v1.114 ANKRD1 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic; Cardiomyopathy, dilated for gene: ANKRD1
BabyScreen+ newborn screening v1.114 ALX4 Tommy Li Added phenotypes {Craniosynostosis 5, susceptibility to} MIM#615529; Parietal foramina 2 MIM# 609597; Frontonasal dysplasia 2 MIM# 613451 for gene: ALX4
BabyScreen+ newborn screening v1.114 ALS2 Tommy Li Added phenotypes Juvenile primary lateral sclerosis (MIM#606353); Infantile onset ascending spastic paralysis (MIM#607225); Juvenile amyotrophic lateral sclerosis 2 (MIM#205100) for gene: ALS2
BabyScreen+ newborn screening v1.114 ALG14 Tommy Li Added phenotypes Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Disorder of N-glycosylation; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036 for gene: ALG14
BabyScreen+ newborn screening v1.114 ALDH3A2 Tommy Li Added phenotypes Sjogren-Larsson syndrome MIM#270200 for gene: ALDH3A2
BabyScreen+ newborn screening v1.114 ALDH18A1 Tommy Li Added phenotypes Spastic paraplegia 9A, autosomal dominant MIM#601162; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism; Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9B, autosomal recessive MIM#616586 for gene: ALDH18A1
BabyScreen+ newborn screening v1.114 AIP Tommy Li Added phenotypes Pituitary adenoma predisposition, MIM# 102200 for gene: AIP
BabyScreen+ newborn screening v1.114 AGTR1 Tommy Li Added phenotypes Renal tubular dysgenesis for gene: AGTR1
BabyScreen+ newborn screening v1.114 AGT Tommy Li Added phenotypes Renal tubular dysgenesis for gene: AGT
BabyScreen+ newborn screening v1.114 AGA Tommy Li Added phenotypes Aspartylglucosaminuria, MIM# 208400 MONDO:0008830 for gene: AGA
BabyScreen+ newborn screening v1.114 ADGRG1 Tommy Li Added phenotypes Polymicrogyria, bilateral frontoparietal, MIM#606854 for gene: ADGRG1
BabyScreen+ newborn screening v1.114 ACTN2 Tommy Li Added phenotypes Cardiomyopathy, familial hypertrophic; Cardiomyopathy, dilated for gene: ACTN2
BabyScreen+ newborn screening v1.114 ACTG1 Tommy Li Added phenotypes Baraitser-Winter syndrome 2MIM#614583; Deafness, autosomal dominant 20/26 MIM#604717 for gene: ACTG1
BabyScreen+ newborn screening v1.114 ACTC1 Tommy Li Added phenotypes Left ventricular noncompaction; Atrial septal defect; Cardiomyopathy, familial hypertrophic; Cardiomyopathy, dilated for gene: ACTC1
BabyScreen+ newborn screening v1.114 ACTB Tommy Li Added phenotypes Baraitser-Winter syndrome; Neutrophil dysfunction and recurrent infection for gene: ACTB
BabyScreen+ newborn screening v1.114 ACO2 Tommy Li Added phenotypes Cerebellar-retinal degeneration, infantile for gene: ACO2
BabyScreen+ newborn screening v1.114 ACE Tommy Li Added phenotypes Renal tubular dysgenesis, MIM# 267430 for gene: ACE
Publications for gene ACE were updated from 16116425; 22095942 to 22095942; 16116425
BabyScreen+ newborn screening v1.114 ABHD12 Tommy Li Added phenotypes Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674 for gene: ABHD12
BabyScreen+ newborn screening v1.114 ABCC9 Tommy Li Added phenotypes Atrial fibrillation, familial; Hypertrichotic osteochondrodysplasia; Cardiomyopathy, dilated for gene: ABCC9
BabyScreen+ newborn screening v1.114 ABCA4 Tommy Li Added phenotypes Cone-rod dystrophy 3, 604116; Fundus flavimaculatus, 248200; Stargardt disease 1, 248200; Retinal dystrophy, early-onset severe, 248200; Retinitis pigmentosa 19, 601718 for gene: ABCA4
BabyScreen+ newborn screening v1.114 ABCA3 Tommy Li Added phenotypes Surfactant metabolism dysfunction, pulmonary, 3, MIM# 610921 for gene: ABCA3
BabyScreen+ newborn screening v1.114 ABCA12 Tommy Li Added phenotypes Ichthyosis, congenital, autosomal recessive 4A (MIM#601277); Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500) for gene: ABCA12
BabyScreen+ newborn screening v1.114 AARS2 Tommy Li Added phenotypes Leukoencephalopathy, and ovarian failure in females for gene: AARS2
BabyScreen+ newborn screening v1.114 AARS Tommy Li Added phenotypes Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; Epileptic encephalopathy, early infantile, 29, MIM# 616339 for gene: AARS
BabyScreen+ newborn screening v1.114 VCL Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: VCL
BabyScreen+ newborn screening v1.114 TTN Tommy Li Added phenotypes Cardiomyopathy, dilated; Centronuclear myopathy for gene: TTN
BabyScreen+ newborn screening v1.114 TRPM4 Tommy Li Added phenotypes Progressive familial heart block, type IB 604559 for gene: TRPM4
BabyScreen+ newborn screening v1.114 TREX1 Tommy Li Added phenotypes Aicardi-Goutieres syndrome 1 MIM#225750 for gene: TREX1
Publications for gene TREX1 were updated from 20301648; 32877590 to 32877590; 20301648
BabyScreen+ newborn screening v1.114 TRDN Tommy Li Added phenotypes Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441 for gene: TRDN
BabyScreen+ newborn screening v1.114 TPM1 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic for gene: TPM1
BabyScreen+ newborn screening v1.114 TNNT2 Tommy Li Added phenotypes Familial hypertrophic cardiomyopathy; Cardiomyopathy, dilated for gene: TNNT2
BabyScreen+ newborn screening v1.114 TNNI3 Tommy Li Added phenotypes Familial hypertrophic cardiomyopathy; Cardiomyopathy, dilated for gene: TNNI3
BabyScreen+ newborn screening v1.114 TNNC1 Tommy Li Added phenotypes Cardiomyopathy, dilated for gene: TNNC1
BabyScreen+ newborn screening v1.114 TECRL Tommy Li Added phenotypes Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021 for gene: TECRL
BabyScreen+ newborn screening v1.114 SPTLC1 Tommy Li Added phenotypes Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400 for gene: SPTLC1
BabyScreen+ newborn screening v1.114 SOX3 Tommy Li Added phenotypes Panhypopituitarism, X-linked MIM#312000 for gene: SOX3
BabyScreen+ newborn screening v1.114 SMARCAL1 Tommy Li Added phenotypes Schimke immune-osseous dysplasia MIM# 242900 for gene: SMARCAL1
BabyScreen+ newborn screening v1.114 SLC9A3 Tommy Li Added phenotypes Diarrhoea 8, secretory sodium, congenital, MiM# 616868 for gene: SLC9A3
BabyScreen+ newborn screening v1.114 SLC25A1 Tommy Li Added phenotypes Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072; Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596 for gene: SLC25A1
BabyScreen+ newborn screening v1.114 SLC16A1 Tommy Li Added phenotypes Hyperinsulinemic hypoglycemia, familial, 7, MIM# 610021; Monocarboxylate transporter 1 deficiency for gene: SLC16A1
BabyScreen+ newborn screening v1.114 SGSH Tommy Li Added phenotypes Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900 for gene: SGSH
BabyScreen+ newborn screening v1.114 SDHC Tommy Li Added phenotypes Hereditary Paraganglioma-Pheochromocytoma Syndromes for gene: SDHC
BabyScreen+ newborn screening v1.114 SDHB Tommy Li Added phenotypes Hereditary Paraganglioma-Pheochromocytoma Syndromes for gene: SDHB
BabyScreen+ newborn screening v1.114 SDHAF2 Tommy Li Added phenotypes Hereditary Paraganglioma-Pheochromocytoma Syndromes for gene: SDHAF2
BabyScreen+ newborn screening v1.114 SAMHD1 Tommy Li Added phenotypes Aicardi-Goutieres syndrome 5, MIM# 612952 for gene: SAMHD1
BabyScreen+ newborn screening v1.114 RNASEH2C Tommy Li Added phenotypes Aicardi-Goutieres syndrome 3, MIM# 610329 for gene: RNASEH2C
BabyScreen+ newborn screening v1.114 RNASEH2B Tommy Li Added phenotypes Aicardi-Goutieres syndrome 2, MIM# 610181 for gene: RNASEH2B
BabyScreen+ newborn screening v1.114 RNASEH2A Tommy Li Added phenotypes Aicardi-Goutieres syndrome 4, MIM# 610333 for gene: RNASEH2A
BabyScreen+ newborn screening v1.114 RBM20 Tommy Li Added phenotypes Cardiomyopathy, dilated, 1DD for gene: RBM20
BabyScreen+ newborn screening v1.114 PKP2 Tommy Li Added phenotypes Arrhythmogenic right ventricular dysplasia 9, MIM# 609040 for gene: PKP2
BabyScreen+ newborn screening v1.114 NLRP3 Tommy Li Added phenotypes Familial cold inflammatory syndrome 1, MIM#120100 Muckle-Wells syndrome, MIM#191900 CINCA syndrome, MIM#607115 Deafness, autosomal dominant 34, with or without inflammation, MIM#617772 Keratoendothelitis fugax hereditaria, MIM#148200 for gene: NLRP3
BabyScreen+ newborn screening v1.114 NAXD Tommy Li Added phenotypes Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321 for gene: NAXD
Publications for gene NAXD were updated from 30576410; 31755961; 32462209; 35231119 to 30576410; 32462209; 31755961; 35231119
BabyScreen+ newborn screening v1.114 MYL3 Tommy Li Added phenotypes Cardiomyopathy, familial hypertrophic, 8 for gene: MYL3
BabyScreen+ newborn screening v1.114 MYL2 Tommy Li Added phenotypes Cardiomyopathy, familial hypertrophic, 10 for gene: MYL2
BabyScreen+ newborn screening v1.114 LMNA Tommy Li Added phenotypes Dilated cardiomyopathy; Emery-Dreifuss muscular dystrophy 2; Charcot-Marie-Tooth disease for gene: LMNA
BabyScreen+ newborn screening v1.114 JUP Tommy Li Added phenotypes Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214 for gene: JUP
BabyScreen+ newborn screening v1.114 IFNGR1 Tommy Li Added phenotypes Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978; Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950 for gene: IFNGR1
BabyScreen+ newborn screening v1.114 IARS Tommy Li Added phenotypes Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093 for gene: IARS
Publications for gene IARS were updated from 27426735; 34194004 to 34194004; 27426735
BabyScreen+ newborn screening v1.114 HNF4A Tommy Li Added phenotypes Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, MIM# 616026; MODY, type I, OMIM # 125850; Hypoglycaemia, hyperinsulinaemic, MIM#125850 for gene: HNF4A
BabyScreen+ newborn screening v1.114 ERCC6L2 Tommy Li Added phenotypes Bone marrow failure syndrome 2, MIM# 615715 for gene: ERCC6L2
BabyScreen+ newborn screening v1.114 DSP Tommy Li Added phenotypes Arrhythmogenic right ventricular dysplasia 8, MIM# 607450 for gene: DSP
BabyScreen+ newborn screening v1.114 DSG2 Tommy Li Added phenotypes Arrhythmogenic right ventricular dysplasia 10, MIM# 610193 for gene: DSG2
BabyScreen+ newborn screening v1.114 DSC2 Tommy Li Added phenotypes Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476 for gene: DSC2
BabyScreen+ newborn screening v1.114 DMD Tommy Li Added phenotypes Duchenne muscular dystrophy MIM#310200 for gene: DMD
Publications for gene DMD were updated from 36278620; 36152336; 35562557; 35307847 to 35562557; 36152336; 35307847; 36278620
BabyScreen+ newborn screening v1.114 DES Tommy Li Added phenotypes Myopathy, myofibrillar; Cardiomyopathy, dilated for gene: DES
BabyScreen+ newborn screening v1.114 CRYAB Tommy Li Added phenotypes Myofibrillar myopathy; Cardiomyopathy, dilated for gene: CRYAB
BabyScreen+ newborn screening v1.114 COQ7 Tommy Li Added phenotypes Coenzyme Q10 deficiency, primary, 8, MIM# 616733 for gene: COQ7
BabyScreen+ newborn screening v1.114 COL3A1 Tommy Li Added phenotypes Ehlers-Danlos syndrome, vascular type, MIM# 130050 for gene: COL3A1
BabyScreen+ newborn screening v1.114 CASQ2 Tommy Li Added phenotypes Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938 for gene: CASQ2
BabyScreen+ newborn screening v1.114 CALM2 Tommy Li Added phenotypes Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990 for gene: CALM2
BabyScreen+ newborn screening v1.114 CALM1 Tommy Li Added phenotypes Ventricular tachycardia, catecholaminergic polymorphic, 4, MIM# 614916 for gene: CALM1
BabyScreen+ newborn screening v1.114 ADAR Tommy Li Added phenotypes Aicardi-Goutieres syndrome 6, MIM# 615010 for gene: ADAR
BabyScreen+ newborn screening v1.114 UGT1A1 Tommy Li Added phenotypes Crigler-Najjar syndrome, type I, MIM# 218800 for gene: UGT1A1
BabyScreen+ newborn screening v1.114 TANGO2 Tommy Li Added phenotypes Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878 for gene: TANGO2
BabyScreen+ newborn screening v1.114 STX16 Tommy Li Added phenotypes Pseudohypoparathyroidism, type IB MIM#603233 for gene: STX16
BabyScreen+ newborn screening v1.114 STK4 Tommy Li Added phenotypes T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM#614868 for gene: STK4
BabyScreen+ newborn screening v1.114 STAR Tommy Li Added phenotypes Congenital lipoid adrenal hyperplasia, MIM#201710 for gene: STAR
BabyScreen+ newborn screening v1.114 SMN1 Tommy Li Added phenotypes Spinal muscular atrophy type 1, MIM#253300 for gene: SMN1
BabyScreen+ newborn screening v1.114 SMARCD2 Tommy Li Added phenotypes Specific granule deficiency 2 MIM#617475 for gene: SMARCD2
BabyScreen+ newborn screening v1.114 SLC4A1 Tommy Li Added phenotypes Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590 for gene: SLC4A1
BabyScreen+ newborn screening v1.114 SLC46A1 Tommy Li Added phenotypes Folate malabsorption, hereditary, MIM# 229050 for gene: SLC46A1
BabyScreen+ newborn screening v1.114 SLC26A4 Tommy Li Added phenotypes Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600 for gene: SLC26A4
BabyScreen+ newborn screening v1.114 SLC26A3 Tommy Li Added phenotypes Diarrhoea 1, secretory chloride, congenital, MIM# 214700 for gene: SLC26A3
BabyScreen+ newborn screening v1.114 SLC25A20 Tommy Li Added phenotypes Carnitine-acylcarnitine translocase deficiency, MIM#212138 for gene: SLC25A20
Publications for gene SLC25A20 were updated from 33085788; 32885845 to 32885845; 33085788
BabyScreen+ newborn screening v1.114 SLC22A5 Tommy Li Added phenotypes Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919 for gene: SLC22A5
BabyScreen+ newborn screening v1.114 SLC18A2 Tommy Li Added phenotypes Parkinsonism-dystonia, infantile, 2, MIM# 618049 for gene: SLC18A2
BabyScreen+ newborn screening v1.114 SLC12A1 Tommy Li Added phenotypes Bartter syndrome, type 1, MIM# 601678 for gene: SLC12A1
BabyScreen+ newborn screening v1.114 SAR1B Tommy Li Added phenotypes Chylomicron retention disease, MIM# 246700 for gene: SAR1B
BabyScreen+ newborn screening v1.114 RYR2 Tommy Li Added phenotypes Arrhythmogenic right ventricular dysplasia 2; Ventricular tachycardia, catecholaminergic polymorphic for gene: RYR2
BabyScreen+ newborn screening v1.114 RNPC3 Tommy Li Added phenotypes Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160 for gene: RNPC3
Publications for gene RNPC3 were updated from 29866761; 32462814; 33650182 to 33650182; 29866761; 32462814
BabyScreen+ newborn screening v1.114 RMRP Tommy Li Added phenotypes Cartilage-hair hypoplasia MIM#250250 for gene: RMRP
BabyScreen+ newborn screening v1.114 RFXAP Tommy Li Added phenotypes Bare lymphocyte syndrome, type II, complementation group D MIM# 209920 for gene: RFXAP
BabyScreen+ newborn screening v1.114 RFX5 Tommy Li Added phenotypes Bare lymphocyte syndrome, type II, complementation group E MIM# 209920; Bare lymphocyte syndrome, type II, complementation group C MIM# 209920 for gene: RFX5
BabyScreen+ newborn screening v1.114 RAG2 Tommy Li Added phenotypes Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457; Combined cellular and humoral immune defects with granulomas MIM# 233650 for gene: RAG2
BabyScreen+ newborn screening v1.114 RAG1 Tommy Li Added phenotypes Omenn syndrome MIM# 603554; Combined cellular and humoral immune defects with granulomas MIM# 233650; Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Severe combined immunodeficiency, B cell-negative MIM# 601457 for gene: RAG1
BabyScreen+ newborn screening v1.114 PTF1A Tommy Li Added phenotypes Pancreatic agenesis 2, MIM# 615935; Pancreatic and cerebellar agenesis, MIM# 609069 for gene: PTF1A
BabyScreen+ newborn screening v1.114 PSTPIP1 Tommy Li Added phenotypes Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416 for gene: PSTPIP1
BabyScreen+ newborn screening v1.114 PROP1 Tommy Li Added phenotypes Pituitary hormone deficiency, combined, 2, MIM#262600 for gene: PROP1
BabyScreen+ newborn screening v1.114 PRKAR1A Tommy Li Added phenotypes Carney complex, type 1, MIM# 160980 for gene: PRKAR1A
BabyScreen+ newborn screening v1.114 PPOX Tommy Li Added phenotypes Variegate porphyria, childhood-onset, MIM# 620483 for gene: PPOX
BabyScreen+ newborn screening v1.114 POU1F1 Tommy Li Added phenotypes Pituitary hormone deficiency, combined, 1 MIM# 613038 for gene: POU1F1
BabyScreen+ newborn screening v1.114 PLPBP Tommy Li Added phenotypes Epilepsy, early-onset, vitamin B6-dependent , MIM#617290 for gene: PLPBP
BabyScreen+ newborn screening v1.114 PC Tommy Li Added phenotypes Pyruvate carboxylase deficiency, MIM# 266150 for gene: PC
BabyScreen+ newborn screening v1.114 PAX3 Tommy Li Added phenotypes Waardenburg syndrome, type 1, OMIM 193500 for gene: PAX3
BabyScreen+ newborn screening v1.114 OTX2 Tommy Li Added phenotypes Pituitary hormone deficiency, combined, 6, MIM# 613986 for gene: OTX2
Publications for gene OTX2 were updated from 18728160; 35320640; 33950863 to 18728160; 33950863; 35320640
BabyScreen+ newborn screening v1.114 OTC Tommy Li Added phenotypes Ornithine transcarbamylase deficiency, MIM#311250 for gene: OTC
BabyScreen+ newborn screening v1.114 OAS1 Tommy Li Added phenotypes Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042 for gene: OAS1
BabyScreen+ newborn screening v1.114 NHEJ1 Tommy Li Added phenotypes Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM#611291 for gene: NHEJ1
BabyScreen+ newborn screening v1.114 NEUROG3 Tommy Li Added phenotypes Diarrhoea 4, malabsorptive, congenital, MIM# 610370 for gene: NEUROG3
Publications for gene NEUROG3 were updated from 32574610; 16855267; 21490072; 28724572 to 32574610; 28724572; 21490072; 16855267
BabyScreen+ newborn screening v1.114 NAGLU Tommy Li Added phenotypes Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920 for gene: NAGLU
BabyScreen+ newborn screening v1.114 MYSM1 Tommy Li Added phenotypes Bone marrow failure syndrome 4, MIM# 618116 for gene: MYSM1
BabyScreen+ newborn screening v1.114 MYH7 Tommy Li Added phenotypes Cardiomyopathy, hypertrophic, 1, MIM# 192600 for gene: MYH7
BabyScreen+ newborn screening v1.114 MPL Tommy Li Added phenotypes Thrombocytopenia, congenital amegakaryocytic, MIM# 604498 for gene: MPL
BabyScreen+ newborn screening v1.114 MLYCD Tommy Li Added phenotypes Malonyl-CoA decarboxylase deficiency, MIM# 248360 for gene: MLYCD
BabyScreen+ newborn screening v1.114 MITF Tommy Li Added phenotypes Waardenburg syndrome, type 2A, MIM# 193510; Deafness for gene: MITF
BabyScreen+ newborn screening v1.114 MARVELD2 Tommy Li Added phenotypes Deafness, autosomal recessive 49, MIM# 610153 for gene: MARVELD2
BabyScreen+ newborn screening v1.114 MAGT1 Tommy Li Added phenotypes Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853) for gene: MAGT1
Publications for gene MAGT1 were updated from 31036665; 31714901 to 31714901; 31036665
BabyScreen+ newborn screening v1.114 MAFB Tommy Li Added phenotypes Multicentric carpotarsal osteolysis syndrome (MIM#166300) for gene: MAFB
BabyScreen+ newborn screening v1.114 LRBA Tommy Li Added phenotypes Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700 for gene: LRBA
Publications for gene LRBA were updated from 22608502; 22721650; 25468195; 26206937; 33155142; 31887391 to 26206937; 33155142; 31887391; 22721650; 22608502; 25468195
BabyScreen+ newborn screening v1.114 LHX4 Tommy Li Added phenotypes Pituitary hormone deficiency, combined, 4, MIM# 262700 for gene: LHX4
BabyScreen+ newborn screening v1.114 LHX3 Tommy Li Added phenotypes Pituitary hormone deficiency, combined, MIM#221750 for gene: LHX3
BabyScreen+ newborn screening v1.114 LAMA2 Tommy Li Added phenotypes Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855 for gene: LAMA2
BabyScreen+ newborn screening v1.114 KCNJ1 Tommy Li Added phenotypes Bartter syndrome, type 2, 241200 for gene: KCNJ1
BabyScreen+ newborn screening v1.114 IL36RN Tommy Li Added phenotypes Psoriasis 14, pustular, MIM# 614204 for gene: IL36RN
BabyScreen+ newborn screening v1.114 IL10RB Tommy Li Added phenotypes Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567 for gene: IL10RB
BabyScreen+ newborn screening v1.114 IL10RA Tommy Li Added phenotypes Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148 for gene: IL10RA
BabyScreen+ newborn screening v1.114 IKZF1 Tommy Li Added phenotypes Immunodeficiency, common variable, 13 MIM# 616873 for gene: IKZF1
BabyScreen+ newborn screening v1.114 IGSF1 Tommy Li Added phenotypes Hypothyroidism, central, and testicular enlargement, MIM# 300888 for gene: IGSF1
BabyScreen+ newborn screening v1.114 IDUA Tommy Li Added phenotypes Mucopolysaccharidosis type 1, MONDO:0001586 for gene: IDUA
BabyScreen+ newborn screening v1.114 IDS Tommy Li Added phenotypes Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900 for gene: IDS
BabyScreen+ newborn screening v1.114 ICOS Tommy Li Added phenotypes Immunodeficiency, common variable, 1 MIM# 607594 for gene: ICOS
BabyScreen+ newborn screening v1.114 HSD11B2 Tommy Li Added phenotypes MONDO:0009025; Apparent mineralocorticoid excess, MIM# 218030 for gene: HSD11B2
BabyScreen+ newborn screening v1.114 HOGA1 Tommy Li Added phenotypes Hyperoxaluria, primary, type III MIM#613616 for gene: HOGA1
Publications for gene HOGA1 were updated from 20797690; 21896830; 22391140 to 22391140; 21896830; 20797690
BabyScreen+ newborn screening v1.114 HMGCL Tommy Li Added phenotypes 3-hydroxy-3-methylglutaric aciduria, MIM#246450 for gene: HMGCL
BabyScreen+ newborn screening v1.114 HLCS Tommy Li Added phenotypes Holocarboxylase synthetase deficiency, MIM#253270 for gene: HLCS
BabyScreen+ newborn screening v1.114 HESX1 Tommy Li Added phenotypes Pituitary hormone deficiency, combined, 5, MIM# 182230 for gene: HESX1
BabyScreen+ newborn screening v1.114 GUSB Tommy Li Added phenotypes Mucopolysaccharidosis VII, MIM#253220 for gene: GUSB
BabyScreen+ newborn screening v1.114 GRHPR Tommy Li Added phenotypes Hyperoxaluria, primary, type II, MIM# 260000 for gene: GRHPR
BabyScreen+ newborn screening v1.114 GNAS Tommy Li Added phenotypes Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism for gene: GNAS
BabyScreen+ newborn screening v1.114 GLRA1 Tommy Li Added phenotypes Hyperekplexia, hereditary 1, autosomal dominant or recessive, MIM#149400 for gene: GLRA1
BabyScreen+ newborn screening v1.114 GHR Tommy Li Added phenotypes Growth hormone insensitivity, partial, MIM# 604271; Laron dwarfism, MIM# 262500 for gene: GHR
BabyScreen+ newborn screening v1.114 GH1 Tommy Li Added phenotypes Growth hormone deficiency, isolated, type IA, MIM# 262400; Kowarski syndrome, MIM# 262650; Growth hormone deficiency, isolated, type II, MIM# 173100 for gene: GH1
BabyScreen+ newborn screening v1.114 GCM2 Tommy Li Added phenotypes Hypoparathyroidism, familial isolated 2, OMIM #618883; Hyperparathyroidism 4, OMIM #617343 for gene: GCM2
Publications for gene GCM2 were updated from 27745835; 20190276; 34967908; 35038313 to 34967908; 20190276; 35038313; 27745835
BabyScreen+ newborn screening v1.114 GCDH Tommy Li Added phenotypes Glutaric aciduria, type I, MIM#231670 for gene: GCDH
BabyScreen+ newborn screening v1.114 GATA3 Tommy Li Added phenotypes Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255 for gene: GATA3
BabyScreen+ newborn screening v1.114 GALNS Tommy Li Added phenotypes Mucopolysaccharidosis IVA, MIM#253000 for gene: GALNS
BabyScreen+ newborn screening v1.114 GALK1 Tommy Li Added phenotypes Galactokinase deficiency with cataracts, MIM#230200 for gene: GALK1
BabyScreen+ newborn screening v1.114 FOXE1 Tommy Li Added phenotypes Bamforth-Lazarus syndrome MIM# 241850 for gene: FOXE1
Publications for gene FOXE1 were updated from 33272083; 2918525; 20453517; 35963604 to 35963604; 2918525; 33272083; 20453517
BabyScreen+ newborn screening v1.114 FGF3 Tommy Li Added phenotypes Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706 for gene: FGF3
BabyScreen+ newborn screening v1.114 FBN1 Tommy Li Added phenotypes Marfan syndrome, MIM# 154700 for gene: FBN1
BabyScreen+ newborn screening v1.114 ETFDH Tommy Li Added phenotypes Glutaric acidemia IIC, MIM#231680 for gene: ETFDH
BabyScreen+ newborn screening v1.114 ETFB Tommy Li Added phenotypes Glutaric acidemia IIB, MIM#231680 for gene: ETFB
BabyScreen+ newborn screening v1.114 ETFA Tommy Li Added phenotypes Glutaric acidaemia IIA, MIM#231680 for gene: ETFA
BabyScreen+ newborn screening v1.114 EPS8 Tommy Li Added phenotypes Autosomal recessive nonsyndromic hearing loss 102, MIM#600205, MONDO:0014428 for gene: EPS8
BabyScreen+ newborn screening v1.114 ENPP1 Tommy Li Added phenotypes Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312; Arterial calcification, generalized, of infancy, 1, MIM# 208000 for gene: ENPP1
BabyScreen+ newborn screening v1.114 ENG Tommy Li Added phenotypes Telangiectasia, hereditary hemorrhagic, type 1 MIM#187300 for gene: ENG
BabyScreen+ newborn screening v1.114 EDNRB Tommy Li Added phenotypes Waardenburg syndrome, type 4A, MIM# 277580 for gene: EDNRB
BabyScreen+ newborn screening v1.114 EDN3 Tommy Li Added phenotypes Waardenburg syndrome, type 4B, MIM# 613265 for gene: EDN3
BabyScreen+ newborn screening v1.114 DPAGT1 Tommy Li Added phenotypes DPAGT1-CDG MONDO:0011964; Congenital disorder of glycosylation, type Ij, MIM# 608093; Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750 for gene: DPAGT1
BabyScreen+ newborn screening v1.114 DNAJC21 Tommy Li Added phenotypes Bone marrow failure syndrome 3, MIM# 617052 for gene: DNAJC21
BabyScreen+ newborn screening v1.114 DGAT1 Tommy Li Added phenotypes Diarrhea 7, protein-losing enteropathy type , MIM# 615863 for gene: DGAT1
BabyScreen+ newborn screening v1.114 DDC Tommy Li Added phenotypes Aromatic L-amino acid decarboxylase deficiency, MIM#608643 for gene: DDC
BabyScreen+ newborn screening v1.114 CYP11A1 Tommy Li Added phenotypes Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, MIM#613743 for gene: CYP11A1
BabyScreen+ newborn screening v1.114 CPT1A Tommy Li Added phenotypes Carnitine palmitoyltransferase I deficiency, MIM#255120 for gene: CPT1A
BabyScreen+ newborn screening v1.114 CPS1 Tommy Li Added phenotypes Carbamoylphosphate synthetase I deficiency, MIM#237300 for gene: CPS1
BabyScreen+ newborn screening v1.114 COQ8A Tommy Li Added phenotypes Coenzyme Q10 deficiency, primary, 4, MIM# 612016 for gene: COQ8A
BabyScreen+ newborn screening v1.114 COQ6 Tommy Li Added phenotypes Coenzyme Q10 deficiency, primary, 6, MIM# 614650 for gene: COQ6
BabyScreen+ newborn screening v1.114 COQ4 Tommy Li Added phenotypes Coenzyme Q10 deficiency, primary, 7, MIM# 616276 for gene: COQ4
BabyScreen+ newborn screening v1.114 COQ2 Tommy Li Added phenotypes Coenzyme Q10 deficiency, primary, 1, MIM# 607426 for gene: COQ2
BabyScreen+ newborn screening v1.114 CIITA Tommy Li Added phenotypes Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920 for gene: CIITA
BabyScreen+ newborn screening v1.114 CD19 Tommy Li Added phenotypes Immunodeficiency, common variable, 3, MIM# 613493 for gene: CD19
BabyScreen+ newborn screening v1.114 CASR Tommy Li Added phenotypes Hypocalcemia, autosomal dominant MIM#601198; Hyperparathyroidism, neonatal MIM#239200 for gene: CASR
BabyScreen+ newborn screening v1.114 CARD11 Tommy Li Added phenotypes Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638 for gene: CARD11
Publications for gene CARD11 were updated from 23374270; 28628108; 23561803; 12818158 to 23374270; 23561803; 28628108; 12818158
BabyScreen+ newborn screening v1.114 CA5A Tommy Li Added phenotypes Hyperammonaemia due to carbonic anhydrase VA deficiency, MIM# 615751 for gene: CA5A
BabyScreen+ newborn screening v1.114 CA2 Tommy Li Added phenotypes Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730 for gene: CA2
BabyScreen+ newborn screening v1.114 BSND Tommy Li Added phenotypes Bartter syndrome, type 4a, MIM# 602522 for gene: BSND
BabyScreen+ newborn screening v1.114 BSCL2 Tommy Li Added phenotypes Berardinelli-Seip lipodystrophy; Lipodystrophy, congenital generalized, type 2, MIM# 269700 for gene: BSCL2
BabyScreen+ newborn screening v1.114 ATP6V1B1 Tommy Li Added phenotypes Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300 for gene: ATP6V1B1
BabyScreen+ newborn screening v1.114 ATP6V0A4 Tommy Li Added phenotypes Distal renal tubular acidosis 3, with or without sensorineural hearing loss, MIM3 602722 for gene: ATP6V0A4
BabyScreen+ newborn screening v1.114 ASL Tommy Li Added phenotypes Argininosuccinic aciduria, MIM#207900 for gene: ASL
BabyScreen+ newborn screening v1.114 ARSB Tommy Li Added phenotypes Mucopolysaccharidosis VI (MPS6, MIM# 253200 for gene: ARSB
BabyScreen+ newborn screening v1.114 ARSA Tommy Li Added phenotypes Metachromatic leukodystrophy, MIM# 250100 for gene: ARSA
BabyScreen+ newborn screening v1.114 ARPC1B Tommy Li Added phenotypes Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, MIM#617718 for gene: ARPC1B
BabyScreen+ newborn screening v1.114 ARG1 Tommy Li Added phenotypes Arginase deficiency, MIM#207800 for gene: ARG1
BabyScreen+ newborn screening v1.114 ALDOB Tommy Li Added phenotypes Fructose intolerance, hereditary, MIM# 229600 for gene: ALDOB
BabyScreen+ newborn screening v1.114 AK2 Tommy Li Added phenotypes Reticular dysgenesis, MIM# 267500; MONDO:0009973 for gene: AK2
BabyScreen+ newborn screening v1.114 AGXT Tommy Li Added phenotypes Hyperoxaluria, primary, type 1, MIM# 259900, MONDO:0009823 for gene: AGXT
BabyScreen+ newborn screening v1.114 ACVRL1 Tommy Li Added phenotypes Telangiectasia, hereditary hemorrhagic, type 2, MIM#600376 for gene: ACVRL1
BabyScreen+ newborn screening v1.114 ACAD9 Tommy Li Added phenotypes Mitochondrial complex I deficiency, nuclear type 20, MIM#611126 for gene: ACAD9
BabyScreen+ newborn screening v1.114 ABCC6 Tommy Li Added phenotypes Arterial calcification, generalized, of infancy, 2, #MIM614473 for gene: ABCC6
Publications for gene ABCC6 were updated from 33005041; 34355424 to 34355424; 33005041
BabyScreen+ newborn screening v1.111 LIG4 Santosh Varughese reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302, 11779494; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.111 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
BabyScreen+ newborn screening v1.110 ELANE Zornitza Stark commented on gene: ELANE: ClinGen: there is little evidence for haploinsufficiency. gnomAD pLI score is zero and there are NMD predicted variants in the population.

Entire gene deletion is not described in the context of neutropenia, including deletion of 19p terminal (encompassing ELANE) (PMID: 33968054).

Maturation arrest, the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated congenital neutropenia. Knock-out of the mutant allele in hematopoietic stem cells derived from SCN patients restores neutrophils maturation (PMID: 3124897).
BabyScreen+ newborn screening v1.110 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Marked gene: WNK1 as ready
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Phenotypes for gene: WNK1 were changed from Neuropathy, hereditary sensory and autonomic, type I to Pseudohypoaldosteronism 2C (PHA2C), MIM#614492
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Marked gene: TRIM28 as ready
BabyScreen+ newborn screening v1.103 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilms tumour, MONDO:0006058, TRIM28-related
Review for gene: TRIM28 was set to GREEN
Added comment: Established gene-disease association, more than 10 individuals reported.

Onset in childhood.

Included for completeness as managed similarly to WT1.
Sources: Expert list
BabyScreen+ newborn screening v1.102 TRHR Zornitza Stark Marked gene: TRHR as ready
BabyScreen+ newborn screening v1.98 SCNN1G Zornitza Stark Marked gene: SCNN1G as ready
BabyScreen+ newborn screening v1.96 RPS7 Zornitza Stark Marked gene: RPS7 as ready
BabyScreen+ newborn screening v1.93 RPL35A Zornitza Stark Marked gene: RPL35A as ready
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Marked gene: REST as ready
BabyScreen+ newborn screening v1.89 REST Zornitza Stark gene: REST was added
gene: REST was added to BabyScreen+ newborn screening. Sources: Expert list
cancer, treatable tags were added to gene: REST.
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to 26551668; 34308104
Phenotypes for gene: REST were set to {Wilms tumor 6, susceptibility to}, MIM# 616806
Review for gene: REST was set to GREEN
Added comment: Established association, more than 10 families reported.

Childhood onset.

Included for completeness as managed similarly to WT1.
Sources: Expert list
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Marked gene: PSTPIP1 as ready
BabyScreen+ newborn screening v1.87 PSTPIP1 Zornitza Stark gene: PSTPIP1 was added
gene: PSTPIP1 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: PSTPIP1.
Mode of inheritance for gene: PSTPIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PSTPIP1 were set to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416
Review for gene: PSTPIP1 was set to GREEN
Added comment: Established gene-disease association.

Onset in childhood.

Treatment: adalimumab and tacrolimus, NSAIDs, corticosteroids, BMT

non-genetic confirmatory testing: no
Sources: Expert list
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Marked gene: PPOX as ready
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata to Variegate porphyria, childhood-onset, MIM# 620483
BabyScreen+ newborn screening v1.83 PPOX Zornitza Stark reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Variegate porphyria, childhood-onset, MIM# 620483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.83 POMC Zornitza Stark Marked gene: POMC as ready
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Marked gene: POLE as ready
BabyScreen+ newborn screening v1.79 NCF4 Zornitza Stark Marked gene: NCF4 as ready
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Marked gene: LPL as ready
BabyScreen+ newborn screening v1.76 LPL Zornitza Stark gene: LPL was added
gene: LPL was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: LPL.
Mode of inheritance for gene: LPL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LPL were set to Lipoprotein lipase deficiency, MIM# 238600
Review for gene: LPL was set to GREEN
Added comment: Established gene-disease association.

Bi-allelic disease is severe and presents in infancy.

Treatment: volanesorsen, dietary fat restriction, lomitapide

Non-genetic confirmatory testing: LPL activity
Sources: Expert list
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Marked gene: LAT as ready
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Marked gene: KLHL3 as ready
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Marked gene: IRF8 as ready
BabyScreen+ newborn screening v1.70 IRF8 Zornitza Stark gene: IRF8 was added
gene: IRF8 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IRF8.
Mode of inheritance for gene: IRF8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRF8 were set to Immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive, MIM# 226990
Review for gene: IRF8 was set to GREEN
Added comment: At least 4 families reported with bi-allelic variants. Gene-disease association also proposed for mono-allelic variants but only two individuals reported.

Recurrent infections presenting in infancy.

Treatment: BMT

Non-genetic confirmatory testing available
Sources: Expert list
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Marked gene: IL10RB as ready
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Phenotypes for gene: IL10RB were changed from Inflammatory bowel disease; Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567 to Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567
BabyScreen+ newborn screening v1.67 IL10RB Zornitza Stark reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Marked gene: IL10 as ready
BabyScreen+ newborn screening v1.65 IGF1 Zornitza Stark Marked gene: IGF1 as ready
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Marked gene: GALNT3 as ready
BabyScreen+ newborn screening v1.62 GALNT3 Zornitza Stark gene: GALNT3 was added
gene: GALNT3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: GALNT3.
Mode of inheritance for gene: GALNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALNT3 were set to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900
Review for gene: GALNT3 was set to GREEN
Added comment: Established gene-disease association.

Onset in infancy/childhood.

Treatment: dietary restriction, phosphate binders, acetazolamide

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase, vitamin D serum levels, urine calcium, phosphate levels, plasma levels of the C-terminal portion of the phosphate-regulating hormone, fibroblast growth factor 23
Sources: Expert list
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Marked gene: FECH as ready
BabyScreen+ newborn screening v1.59 F13B Zornitza Stark Marked gene: F13B as ready
BabyScreen+ newborn screening v1.56 F10 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity: for review. Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex); to: Well established gene-disease association.

Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex)
BabyScreen+ newborn screening v1.56 ERCC4 Zornitza Stark Marked gene: ERCC4 as ready
BabyScreen+ newborn screening v1.54 CYP7B1 Zornitza Stark Marked gene: CYP7B1 as ready
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Marked gene: CUL3 as ready
BabyScreen+ newborn screening v1.50 CUL3 Zornitza Stark gene: CUL3 was added
gene: CUL3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: CUL3.
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CUL3 were set to Pseudohypoaldosteronism, type IIE 614496
Review for gene: CUL3 was set to GREEN
Added comment: Established gene-disease association.

Variants in this gene also cause a neurodevelopmental disorder; however, there is some genotype-phenotype correlation literature to help distinguish the two.

Results in hyperkalaemia and development of hypertension. However, the onset of hypertension is generally later in life.

Treatment: thiazide diuretics normalise biochemical abnormalities
Sources: Expert list
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Marked gene: COQ6 as ready
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Phenotypes for gene: COQ6 were changed from Nephrotic syndrome with sensorineural deafness; Coenzyme Q10 deficiency, primary, 6, MIM# 614650 to Coenzyme Q10 deficiency, primary, 6, MIM# 614650
BabyScreen+ newborn screening v1.46 COQ6 Zornitza Stark reviewed gene: COQ6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 6 MIM#614650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Marked gene: COQ2 as ready
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from Coenzyme Q10 deficiency, primary, 1, MIM# 607426; Coenzyme Q10 deficiency, primary, 1 to Coenzyme Q10 deficiency, primary, 1, MIM# 607426
BabyScreen+ newborn screening v1.44 COQ2 Zornitza Stark reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 1, MIM# 607426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Marked gene: CHRNB1 as ready
BabyScreen+ newborn screening v1.43 CFI Zornitza Stark Marked gene: CFI as ready
BabyScreen+ newborn screening v1.41 CFH Zornitza Stark Marked gene: CFH as ready
BabyScreen+ newborn screening v1.39 CFD Zornitza Stark Marked gene: CFD as ready
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Marked gene: CEBPE as ready
BabyScreen+ newborn screening v1.34 C3 Zornitza Stark Marked gene: C3 as ready
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Marked gene: C2 as ready
BabyScreen+ newborn screening v1.31 C2 Zornitza Stark gene: C2 was added
gene: C2 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2 were set to 31421540
Phenotypes for gene: C2 were set to C2 deficiency, MIM# 217000
Review for gene: C2 was set to GREEN
Added comment: Established gene-disease association.

Can present with severe early infections in infancy/childhood.

Later manifestations include autoimmune phenomena.

Treatment: pneumococcal, meningococcal, haemophilus influenzae vaccines

Non-genetic confirmatory tests: complement levels
Sources: Expert list
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark Marked gene: APOA5 as ready
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark gene: APOA5 was added
gene: APOA5 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable tags were added to gene: APOA5.
Mode of inheritance for gene: APOA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOA5 were set to 23307945; 31390500
Phenotypes for gene: APOA5 were set to Hyperchylomicronaemia, late-onset, MIM# 144650
Review for gene: APOA5 was set to RED
Added comment: Established gene-disease association.

Variable age of onset, many of the reported individuals are adults.

Treatment: Volanesorsen
Sources: Expert list
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Marked gene: AP3D1 as ready
BabyScreen+ newborn screening v1.28 AP3D1 Zornitza Stark gene: AP3D1 was added
gene: AP3D1 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, haematological tags were added to gene: AP3D1.
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3D1 were set to 26744459; 9697856; 30472485; 36445457
Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050
Review for gene: AP3D1 was set to AMBER
Added comment: Four individuals from two unrelated families and a mouse model. Borderline gene-disease association.

New case report 36445457, proband presenting with SNHL and questionable other subtle features of HPS, homozygous missense variant (VOUS).

Onset in infancy.

Treatable: BMT for immunodeficiency.
Sources: Expert list
BabyScreen+ newborn screening v1.27 AMACR Zornitza Stark Marked gene: AMACR as ready
BabyScreen+ newborn screening v1.24 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark Marked gene: TRAC as ready
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark gene: TRAC was added
gene: TRAC was added to BabyScreen+ newborn screening. Sources: Expert Review
founder, technically challenging tags were added to gene: TRAC.
Mode of inheritance for gene: TRAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAC were set to 21206088
Phenotypes for gene: TRAC were set to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387
Review for gene: TRAC was set to RED
Added comment: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001)

Also note annotation issues in certain variant curation and annotation tools.
Sources: Expert Review
BabyScreen+ newborn screening v1.20 IGHM Zornitza Stark changed review comment from: RefSeq annotation issues.; to: RefSeq annotation issues. Specific rescue loop built to capture variants.
BabyScreen+ newborn screening v1.17 CYP21A2 Zornitza Stark edited their review of gene: CYP21A2: Added comment: Part of Victorian sNBS, therefore include, although technically challenging.; Changed rating: GREEN
BabyScreen+ newborn screening v1.14 KCNA5 Zornitza Stark Marked gene: KCNA5 as ready
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Marked gene: GABRG2 as ready
BabyScreen+ newborn screening v1.11 GABRG2 Zornitza Stark reviewed gene: GABRG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 74 618396, Epilepsy, generalized, with febrile seizures plus, type 3 607681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.11 DKC1 Zornitza Stark Marked gene: DKC1 as ready
BabyScreen+ newborn screening v1.9 CDKN2A Zornitza Stark Marked gene: CDKN2A as ready
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Marked gene: BMPR2 as ready
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Phenotypes for gene: BMPR2 were changed from Pulmonary hypertension, familial primary to Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600
BabyScreen+ newborn screening v1.5 BMPR2 Zornitza Stark reviewed gene: BMPR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.4 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Marked gene: AIP as ready
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Phenotypes for gene: AIP were changed from Pituitary adenoma to Pituitary adenoma predisposition, MIM# 102200
BabyScreen+ newborn screening v1.1 AIP Zornitza Stark reviewed gene: AIP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary adenoma predisposition, MIM# 102200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.2175 COL4A6 Zornitza Stark edited their review of gene: COL4A6: Added comment: Further review of PMID:33840813;

Family A:
- Proband is hemi for COL4A6 and het for GJB2. Mother is het for COL4A6
- hypothesised that in the proband is more severe than the parents due to additive effects of his two variants however, mother's audiometric data was unavailable to confirm this.

Family B:
- Variant does not segregate within family with the proband being WT in this gene
- NM_001287758.1: c.3272G>C is the mutation however, it appears to be an annotation error as it corresponds to NC_000023.11:g.108171443 in GRCh38. At that position, the c. is T not G and the amino acid residue is Val, not Gly.

In addition, there is a missense affecting Gly of GXY in gnomad v3 with 38 hemis.; Changed rating: RED; Changed publications: 33840813; Changed phenotypes: Deafness, X-linked 6 MIM#300914; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.2175 MT-RNR1 Zornitza Stark changed review comment from: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G
m.1005T>C
m.1095T>C

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review; to: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G and m.1494C>T

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review
BabyScreen+ newborn screening v0.2175 PDP1 Zornitza Stark Marked gene: PDP1 as ready
BabyScreen+ newborn screening v0.2173 DLAT Zornitza Stark Marked gene: DLAT as ready
BabyScreen+ newborn screening v0.2171 PDHB Zornitza Stark Marked gene: PDHB as ready
BabyScreen+ newborn screening v0.2169 TUBB4B Zornitza Stark Marked gene: TUBB4B as ready
BabyScreen+ newborn screening v0.2168 SUFU Zornitza Stark Marked gene: SUFU as ready
BabyScreen+ newborn screening v0.2167 SLITRK6 Zornitza Stark Marked gene: SLITRK6 as ready
BabyScreen+ newborn screening v0.2166 PAX5 Zornitza Stark Marked gene: PAX5 as ready
BabyScreen+ newborn screening v0.2165 MPZL2 Zornitza Stark Marked gene: MPZL2 as ready
BabyScreen+ newborn screening v0.2164 LMX1A Zornitza Stark Marked gene: LMX1A as ready
BabyScreen+ newborn screening v0.2163 GREB1L Zornitza Stark Marked gene: GREB1L as ready
BabyScreen+ newborn screening v0.2162 NLRP3 Zornitza Stark Marked gene: NLRP3 as ready
BabyScreen+ newborn screening v0.2161 NLRP3 Zornitza Stark gene: NLRP3 was added
gene: NLRP3 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP3 were set to 25038238
Phenotypes for gene: NLRP3 were set to Familial cold inflammatory syndrome 1, MIM#120100 Muckle-Wells syndrome, MIM#191900 CINCA syndrome, MIM#607115 Deafness, autosomal dominant 34, with or without inflammation, MIM#617772 Keratoendothelitis fugax hereditaria, MIM#148200
Review for gene: NLRP3 was set to AMBER
Added comment: Established gene-disease associations.

Variants in this gene cause a spectrum of clinical phenotypes, ranging from onset in infancy to adult-onset, with variable severity. Genotype-phenotype correlation is unclear, hence not suitable for inclusion at this time.

Treatment: corticosteroids, anakinra, rilonacept and canakinumab.

Non-genetic confirmatory testing: no.
Sources: Expert Review
BabyScreen+ newborn screening v0.2158 AMT Zornitza Stark edited their review of gene: AMT: Added comment: Severe infantile forms: treatment does not currently alter outcomes.

Attenuated forms can have onset in childhood, therapy with sodium benzoate and NMDA (The N-methyl-D-aspartate receptor) receptor site antagonists (dextromethorphan, ketamine) but uncertainty about effectiveness.; Changed rating: AMBER; Changed publications: 35683414
BabyScreen+ newborn screening v0.2156 GLDC Zornitza Stark changed review comment from: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.; to: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.

However, the effectiveness of treatment is not established, PMID 35683414 for a recent review.
BabyScreen+ newborn screening v0.2155 GLDC Zornitza Stark commented on gene: GLDC: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.
BabyScreen+ newborn screening v0.2154 SAMHD1 Zornitza Stark reviewed gene: SAMHD1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2153 CYP27A1 Zornitza Stark edited their review of gene: CYP27A1: Added comment: Average age of onset is in late childhood, but a proportion would have onset < 5yo and early treatment beneficial.; Changed rating: GREEN; Changed publications: 24442603
BabyScreen+ newborn screening v0.2151 SGSH Zornitza Stark reviewed gene: SGSH: Rating: AMBER; Mode of pathogenicity: None; Publications: 31044143; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2151 GPR161 Zornitza Stark Marked gene: GPR161 as ready
BabyScreen+ newborn screening v0.2150 CTR9 Zornitza Stark Marked gene: CTR9 as ready
BabyScreen+ newborn screening v0.2149 ALK Zornitza Stark Marked gene: ALK as ready
BabyScreen+ newborn screening v0.2148 SUFU Lilian Downie gene: SUFU was added
gene: SUFU was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUFU were set to PMID: 29186568
Phenotypes for gene: SUFU were set to {Medulloblastoma} MIM#155255
Penetrance for gene: SUFU were set to Incomplete
Review for gene: SUFU was set to RED
Added comment: Medullobastoma 1st year of life
incomplete penetrance
worse outcomes
no determined screening protocol
Sources: Expert list
BabyScreen+ newborn screening v0.2148 GPR161 Lilian Downie gene: GPR161 was added
gene: GPR161 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to PMID: 31609649
Phenotypes for gene: GPR161 were set to Medulloblastoma predisposition syndrome MIM#155255
Penetrance for gene: GPR161 were set to Incomplete
Review for gene: GPR161 was set to RED
Added comment: Increased risk of medulloblastoma at <3yrs
Also identified in population and healthy parents
Sources: Expert list
BabyScreen+ newborn screening v0.2148 CTR9 Lilian Downie gene: CTR9 was added
gene: CTR9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to PMID: 32412586
Phenotypes for gene: CTR9 were set to Wilms tumour predisposition
Penetrance for gene: CTR9 were set to Incomplete
Review for gene: CTR9 was set to RED
Added comment: 9/14 germline variant developed Wilms (in 4 families)
Red due to reduced penetrance
Sources: Expert list
BabyScreen+ newborn screening v0.2148 ALK Lilian Downie gene: ALK was added
gene: ALK was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 22071890
Phenotypes for gene: ALK were set to {Neuroblastoma, susceptibility to, 3} MIM#613014
Penetrance for gene: ALK were set to Incomplete
Review for gene: ALK was set to RED
Added comment: Reduced penetrance
Not clear guideline on management if detected
Sources: Expert list
BabyScreen+ newborn screening v0.2148 TUBB4B Lilian Downie gene: TUBB4B was added
gene: TUBB4B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4B were set to PMID: 29198720, 35240325
Phenotypes for gene: TUBB4B were set to Leber congenital amaurosis with early-onset deafness MIM#617879
Review for gene: TUBB4B was set to RED
Added comment: The TUBB4B gene has been associated with autosomal dominant Leber congenital amaurosis with early-onset deafness
Not consistently hearing phenotype <5years therefore excluded
Sources: Expert list
BabyScreen+ newborn screening v0.2148 MPZL2 Lilian Downie gene: MPZL2 was added
gene: MPZL2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: MPZL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPZL2 were set to PMID: 29982980, 29961571, 35734045,33234333
Phenotypes for gene: MPZL2 were set to Deafness, autosomal recessive 111 MIM#618145
Review for gene: MPZL2 was set to RED
Added comment: Most cases are pre-lingual but 29961571, 35734045 report adult onset so I think should be excluded based on variability of age of onset
Sources: Expert list
BabyScreen+ newborn screening v0.2148 CRYM Zornitza Stark Marked gene: CRYM as ready
BabyScreen+ newborn screening v0.2147 COL4A6 Zornitza Stark Marked gene: COL4A6 as ready
BabyScreen+ newborn screening v0.2147 COL4A6 Zornitza Stark Added comment: Comment when marking as ready: Agree, report in males only.
BabyScreen+ newborn screening v0.2146 CLDN9 Zornitza Stark Marked gene: CLDN9 as ready
BabyScreen+ newborn screening v0.2145 CEP250 Zornitza Stark Marked gene: CEP250 as ready
BabyScreen+ newborn screening v0.2144 ABHD12 Zornitza Stark Marked gene: ABHD12 as ready
BabyScreen+ newborn screening v0.2143 CD164 Zornitza Stark Marked gene: CD164 as ready
BabyScreen+ newborn screening v0.2142 AP1B1 Zornitza Stark Marked gene: AP1B1 as ready
BabyScreen+ newborn screening v0.2141 LMX1A Lilian Downie gene: LMX1A was added
gene: LMX1A was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: LMX1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMX1A were set to PMID: 29754270
Phenotypes for gene: LMX1A were set to Deafness, autosomal dominant 7 MIM#601412
Review for gene: LMX1A was set to RED
Added comment: Age of onset too variable
Sources: Expert list
BabyScreen+ newborn screening v0.2141 GREB1L Lilian Downie gene: GREB1L was added
gene: GREB1L was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to PMID: 29955957, 32585897
Phenotypes for gene: GREB1L were set to Deafness, autosomal dominant 80 MIM#619274
Review for gene: GREB1L was set to GREEN
Added comment: Congenital hearing impairment with cochlear abnormalities
This gene also causes Renal hypodysplasia/aplasia 3 MIM#617805 with no clear difference in mutation spectrum
Sources: Expert list
BabyScreen+ newborn screening v0.2141 CRYM Lilian Downie gene: CRYM was added
gene: CRYM was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CRYM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYM were set to PMID: 12471561, 32742378
Phenotypes for gene: CRYM were set to Deafness, autosomal dominant 40 MIM#616357
Review for gene: CRYM was set to RED
Added comment: Dominant hearing loss
One paper infant onset, the other all adult onset
Sources: Expert list
BabyScreen+ newborn screening v0.2141 COL4A6 Lilian Downie gene: COL4A6 was added
gene: COL4A6 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: COL4A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: COL4A6 were set to PMID: 33840813, PMID: 23714752
Phenotypes for gene: COL4A6 were set to Deafness, X-linked 6 MIM#300914
Review for gene: COL4A6 was set to GREEN
Added comment: Pre-lingual or congenital deafness in males
consider not reporting in females (may have adult onset hearing impairment)
Sources: Expert list
BabyScreen+ newborn screening v0.2141 CEP250 Lilian Downie gene: CEP250 was added
gene: CEP250 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CEP250 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP250 were set to PMID: 34223797, PMID: 29718797, PMID: 30459346, PMID: 28005958
Phenotypes for gene: CEP250 were set to Cone-rod dystrophy and hearing loss 2 MIM#618358
Review for gene: CEP250 was set to RED
Added comment: Hearing loss and RP
Atypical Usher phenotype
Age of onset and penetrance of hearing loss component is variable and seeing as this is the treatable component have excluded from list
Sources: Expert list
BabyScreen+ newborn screening v0.2141 ABHD12 Lilian Downie gene: ABHD12 was added
gene: ABHD12 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ABHD12 were set to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674
Review for gene: ABHD12 was set to RED
Added comment: Age of onset not consistently under 5 for treatable elements such as hearing loss.
Sources: Expert list
BabyScreen+ newborn screening v0.2141 CD164 Lilian Downie gene: CD164 was added
gene: CD164 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CD164 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CD164 were set to Deafness, autosomal dominant 66 MIM#616969
Review for gene: CD164 was set to RED
Added comment: Green in our mendeliome/deafness but limited evidence by clingen
variable age of onset from newborn to 20's reason for exclusion
Sources: Expert list
BabyScreen+ newborn screening v0.2141 AP1B1 Lilian Downie gene: AP1B1 was added
gene: AP1B1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1B1 were set to PMID:31630791, 31630788, 33452671
Phenotypes for gene: AP1B1 were set to Keratitis-ichthyosis-deafness syndrome, autosomal recessive MIM#242150
Review for gene: AP1B1 was set to GREEN
Added comment: Icthyosis
progressive hearing loss (childhood) often detected newborn screening
photophobia
corneal scarring/keratitis
variable dev delay
part of copper metabolism pathway but no proven treatment
Sources: Expert list
BabyScreen+ newborn screening v0.2140 LAMP2 Zornitza Stark edited their review of gene: LAMP2: Added comment: Treatment is currently symptomatic.

On watch list with regards to specific treatment/clinical trials.; Changed rating: AMBER
BabyScreen+ newborn screening v0.2140 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from Laing early-onset distal myopathy, MONDO:0008050; Cardiomyopathy, hypertrophic, 1, OMIM:192600; Dilated cardiomyopathy 1S, MONDO:0013262; Hypertrophic cardiomyopathy 1, MONDO:0008647; Laing distal myopathy, OMIM:160500; Left ventricular noncompaction 5, OMIM:613426; Cardiomyopathy, dilated, 1S, OMIM:613426 to Cardiomyopathy, hypertrophic, 1, MIM# 192600
BabyScreen+ newborn screening v0.2137 MYH7 Zornitza Stark Tag cardiac tag was added to gene: MYH7.
Tag treatable tag was added to gene: MYH7.
BabyScreen+ newborn screening v0.2137 MYH7 Zornitza Stark edited their review of gene: MYH7: Added comment: Discussed with paedric cardiologist: include bi-allelic cardiac variants as can present in the neonatal period with an aggressive cardiomyopathy and associated arrhythmias.; Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, hypertrophic, 1, MIM# 192600; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2135 KCNJ2 Zornitza Stark edited their review of gene: KCNJ2: Added comment: Include for Andersen syndrome and Long QT-associated variants only. Onset in infancy.; Changed rating: GREEN; Changed phenotypes: Andersen syndrome MIM#170390
BabyScreen+ newborn screening v0.2134 TRDN Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
BabyScreen+ newborn screening v0.2133 TECRL Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with a paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
BabyScreen+ newborn screening v0.2133 TECRL Zornitza Stark edited their review of gene: TECRL: Changed rating: AMBER; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
BabyScreen+ newborn screening v0.2132 SCN5A Zornitza Stark changed review comment from: These two associations have been rated as 'strong actionability' in paediatric patients by ClinGen.

Note LongQT generally has symptom onset in adolescence and Brugada typically presents in adulthood.

For review: age of onset and penetrance.; to: These two associations have been rated as 'strong actionability' in paediatric patients by ClinGen.

Note LongQT generally has symptom onset in adolescence and Brugada typically presents in adulthood.

Reviewed with paediatric cardiologist: generally later age of onset, does not fulfil criteria for gNBS.
BabyScreen+ newborn screening v0.2131 PRKG1 Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).
Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).

Discussed with a paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
Sources: ClinGen
BabyScreen+ newborn screening v0.2130 MYH11 Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.

Reviewed with a paediatric cardiologist: variable penetrance and age of onset, does not meet criteria for gNBS.
BabyScreen+ newborn screening v0.2129 LOX Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.
Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.

Discussed with paediatric cardiologist: variable penetrance and age of onset, does not fit with criteria for gNBS.
Sources: ClinGen
BabyScreen+ newborn screening v0.2128 JUP Zornitza Stark changed review comment from: Screen for bi-allelic disease as can be earlier onset, more severe.; to: Discussed potentially just screening for bi-allelic disease as can be earlier onset, more severe.

Discussed further with a paediatric cardiologist: variable age of onset and penetrance, therefore does not meet criteria.
BabyScreen+ newborn screening v0.2127 DSP Zornitza Stark changed review comment from: Screen for bi-allelic disease as can be more severe, earlier onset.; to: Discussed screening for bi-allelic disease as can be more severe, earlier onset.

Also discussed with paediatric cardiologist: variable age of onset and penetrance, exclude.
BabyScreen+ newborn screening v0.2126 CASQ2 Zornitza Stark changed review comment from: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

; to: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Reviewed with paediatric cardiologist: variable penetrance and age of onset.
BabyScreen+ newborn screening v0.2125 CALM3 Zornitza Stark Phenotypes for gene: CALM3 were changed from Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782; Long QT syndrome 16, MIM#618782 to Long QT syndrome 16, MIM#618782
BabyScreen+ newborn screening v0.2124 CALM3 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Exclude for CPVT: association has moderate evidence, there are issues with penetrance, and treatment is generally only recommended in symptomatic individuals.
Sources: ClinGen
BabyScreen+ newborn screening v0.2123 CALM2 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.
BabyScreen+ newborn screening v0.2123 CALM1 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.
BabyScreen+ newborn screening v0.2123 VAMP1 Zornitza Stark Marked gene: VAMP1 as ready
BabyScreen+ newborn screening v0.2119 TUBB1 Zornitza Stark Marked gene: TUBB1 as ready
BabyScreen+ newborn screening v0.2118 TUBB1 Zornitza Stark gene: TUBB1 was added
gene: TUBB1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TUBB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB1 were set to 30446499
Phenotypes for gene: TUBB1 were set to Congenital hypothyroidism, MONDO:0018612, TUBB1-related; Macrothrombocytopenia, autosomal dominant, TUBB1-related, OMIM # 613112
Review for gene: TUBB1 was set to GREEN
Added comment: At least 3 families reported with congenital hypothyroidism associated with TUBB1 variants. Platelet abnormalities reported.

Treatment: thyroxine.

Non-genetic confirmatory testing: TFTs, blood film.
Sources: Expert list
BabyScreen+ newborn screening v0.2117 SLC26A7 Zornitza Stark Marked gene: SLC26A7 as ready
BabyScreen+ newborn screening v0.2116 SLC26A7 Zornitza Stark gene: SLC26A7 was added
gene: SLC26A7 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: SLC26A7.
Mode of inheritance for gene: SLC26A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A7 were set to 34780050; 32486989; 31372509; 30333321
Phenotypes for gene: SLC26A7 were set to Congenital hypothyroidism, MONDO:0018612, SLC26A7-related
Review for gene: SLC26A7 was set to GREEN
Added comment: More than 10 unrelated families reported.

Congenital hypothyroidism.

Treatment: thyroxine.

Should be detected through standard NBS.
Sources: Expert list
BabyScreen+ newborn screening v0.2115 OTX2 Zornitza Stark Marked gene: OTX2 as ready
BabyScreen+ newborn screening v0.2114 OTX2 Zornitza Stark gene: OTX2 was added
gene: OTX2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: OTX2.
Mode of inheritance for gene: OTX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTX2 were set to 18728160; 35320640; 33950863
Phenotypes for gene: OTX2 were set to Pituitary hormone deficiency, combined, 6, MIM# 613986
Review for gene: OTX2 was set to GREEN
Added comment: Variants in this gene have been associated with pituitary hormone deficiency with or without microphthalmia, including of TSH.

Congenital onset.

Microphthalmia would present clinically in the newborn period. Infants with TSH deficiency should be detected by standard NBS.

Treatment: thyroxine and other hormone replacements.
Sources: Expert list
BabyScreen+ newborn screening v0.2113 HESX1 Zornitza Stark Marked gene: HESX1 as ready
BabyScreen+ newborn screening v0.2113 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from Septooptic dysplasia, MIM# 182230; Pituitary hypoplasia to Pituitary hormone deficiency, combined, 5, MIM# 182230
BabyScreen+ newborn screening v0.2110 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 5, MIM# 182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2110 CDCA8 Zornitza Stark Marked gene: CDCA8 as ready
BabyScreen+ newborn screening v0.2109 CDCA8 Zornitza Stark gene: CDCA8 was added
gene: CDCA8 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: CDCA8.
Mode of inheritance for gene: CDCA8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CDCA8 were set to 28025328; 29546359
Phenotypes for gene: CDCA8 were set to Congenital hypothyroidism, MONDO:0018612, CDCA8-related
Review for gene: CDCA8 was set to GREEN
Added comment: 4 families (1 with bilallelic variants [parent affected as HTZ], 3 with monoallelic variants) with functional evidence of variants.

Treatment: thyroxine

Likely to be detected on standard NBS.
Sources: Expert list
BabyScreen+ newborn screening v0.2108 FOXN1 Zornitza Stark Marked gene: FOXN1 as ready
BabyScreen+ newborn screening v0.2104 TMEM38B Zornitza Stark Marked gene: TMEM38B as ready
BabyScreen+ newborn screening v0.2103 TMEM38B Zornitza Stark gene: TMEM38B was added
gene: TMEM38B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TMEM38B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM38B were set to 23054245; 28323974
Phenotypes for gene: TMEM38B were set to Osteogenesis imperfecta, type XIV , MIM#615066
Review for gene: TMEM38B was set to GREEN
Added comment: More than 10 families reported.

Variable severity, onset of fractures generally in infancy.

Treatment: bisphosphanates; improvement in BMD reported.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2102 SPARC Zornitza Stark Marked gene: SPARC as ready
BabyScreen+ newborn screening v0.2102 SPARC Zornitza Stark Gene: sparc has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2102 SPARC Zornitza Stark gene: SPARC was added
gene: SPARC was added to Baby Screen+ newborn screening. Sources: Expert list
skeletal tags were added to gene: SPARC.
Mode of inheritance for gene: SPARC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPARC were set to 26027498; 34462290
Phenotypes for gene: SPARC were set to Osteogenesis imperfecta, type XVII, MIM# 616507
Review for gene: SPARC was set to RED
Added comment: Established gene-disease association, 5 families reported.

Onset of fractures in infancy.

Prominent neuromuscular features, MRI brain changes; some with ID.

Treatment: bisphosphanates are generally used in OI but the case reports where these have been used do not seem terribly convincing in terms of response/improvement.

Exclude for now.
Sources: Expert list
BabyScreen+ newborn screening v0.2101 SP7 Zornitza Stark Marked gene: SP7 as ready
BabyScreen+ newborn screening v0.2097 SERPINH1 Zornitza Stark Marked gene: SERPINH1 as ready
BabyScreen+ newborn screening v0.2095 SERPINF1 Zornitza Stark Marked gene: SERPINF1 as ready
BabyScreen+ newborn screening v0.2093 PPIB Zornitza Stark Marked gene: PPIB as ready
BabyScreen+ newborn screening v0.2092 PLOD2 Zornitza Stark Marked gene: PLOD2 as ready
BabyScreen+ newborn screening v0.2091 P3H1 Zornitza Stark Marked gene: P3H1 as ready
BabyScreen+ newborn screening v0.2089 MESD Zornitza Stark Marked gene: MESD as ready
BabyScreen+ newborn screening v0.2087 KDELR2 Zornitza Stark Marked gene: KDELR2 as ready
BabyScreen+ newborn screening v0.2086 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, skeletal tags were added to gene: KDELR2.
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KDELR2 were set to Osteogenesis imperfecta 21, MIM# 619131
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.

Onset in infancy.

Improvement reported with bisphosphanates, similar to other OI.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2085 FKBP10 Zornitza Stark Marked gene: FKBP10 as ready
BabyScreen+ newborn screening v0.2084 FKBP10 Zornitza Stark gene: FKBP10 was added
gene: FKBP10 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: FKBP10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP10 were set to 34173012
Phenotypes for gene: FKBP10 were set to Osteogenesis imperfecta, type XI, OMIM:610968
Review for gene: FKBP10 was set to GREEN
Added comment: Well established gene-disease association.

Early-onset bone fractures and progressive skeletal deformities.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2083 BMP1 Zornitza Stark Marked gene: BMP1 as ready
BabyScreen+ newborn screening v0.2082 BMP1 Zornitza Stark gene: BMP1 was added
gene: BMP1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: BMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BMP1 were set to 33818922
Phenotypes for gene: BMP1 were set to Osteogenesis imperfecta, type XIII , MIM#614856
Review for gene: BMP1 was set to GREEN
Added comment: Rare cause of OI. 20 families reported.

Treatment: bisphosphanates.
Sources: Expert list
BabyScreen+ newborn screening v0.2081 PTH1R Zornitza Stark changed review comment from: Variants in this gene are associated with a range of skeletal disorder.

Wide variability in severity, with BOCD manifesting antenatally.

No specific treatment.; to: Variants in this gene are associated with a range of skeletal disorders.

Wide variability in severity, with BOCD manifesting antenatally.

No specific treatment.
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Marked gene: SARS as ready
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Gene: sars has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Classified gene: SARS as Red List (low evidence)
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Gene: sars has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Marked gene: SCARB2 as ready
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Classified gene: SCARB2 as Red List (low evidence)
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2079 SERPING1 Zornitza Stark Marked gene: SERPING1 as ready
BabyScreen+ newborn screening v0.2078 SGPL1 Zornitza Stark Marked gene: SGPL1 as ready
BabyScreen+ newborn screening v0.2077 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Marked gene: SMARCD2 as ready
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Classified gene: SMARCD2 as Green List (high evidence)
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2075 SMARCD2 Zornitza Stark Tag treatable tag was added to gene: SMARCD2.
Tag immunological tag was added to gene: SMARCD2.
BabyScreen+ newborn screening v0.2075 SMARCD2 Zornitza Stark reviewed gene: SMARCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Specific granule deficiency 2 MIM#617475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2075 SNX10 Zornitza Stark Marked gene: SNX10 as ready
BabyScreen+ newborn screening v0.2074 SORD Zornitza Stark Marked gene: SORD as ready
BabyScreen+ newborn screening v0.2073 SOX3 Zornitza Stark Marked gene: SOX3 as ready
BabyScreen+ newborn screening v0.2072 SOX3 Zornitza Stark reviewed gene: SOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Panhypopituitarism, X-linked MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.2072 STAT1 Zornitza Stark Marked gene: STAT1 as ready
BabyScreen+ newborn screening v0.2070 STIM1 Zornitza Stark Marked gene: STIM1 as ready
BabyScreen+ newborn screening v0.2069 STK4 Zornitza Stark Marked gene: STK4 as ready
BabyScreen+ newborn screening v0.2068 STK4 Zornitza Stark reviewed gene: STK4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM#614868; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2068 STX16 Zornitza Stark Marked gene: STX16 as ready
BabyScreen+ newborn screening v0.2067 SYT2 Zornitza Stark Marked gene: SYT2 as ready
BabyScreen+ newborn screening v0.2065 TBL1X Zornitza Stark Marked gene: TBL1X as ready
BabyScreen+ newborn screening v0.2064 TF Zornitza Stark Marked gene: TF as ready
BabyScreen+ newborn screening v0.2063 SARS Lilian Downie gene: SARS was added
gene: SARS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to PMID:34570399, PMID: 34194004
Phenotypes for gene: SARS were set to Neurodevelopmental disorder with microcephaly, ataxia, and seizures MIM#617709
Review for gene: SARS was set to RED
Added comment: developmental delay, deafness, cardiomyopathy, epilepsy, and severe febrile decompensations
Rx serine supplementation - limited evidence and sounds supportive only
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SCARB2 Lilian Downie gene: SCARB2 was added
gene: SCARB2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SCARB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCARB2 were set to PMID: 34337151, PMID: 35346091, PMID: 26677510
Phenotypes for gene: SCARB2 were set to Epilepsy, progressive myoclonic 4, with or without renal failure MIM#254900
Review for gene: SCARB2 was set to RED
Added comment: Onset not <5
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SERPING1 Lilian Downie gene: SERPING1 was added
gene: SERPING1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SERPING1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SERPING1 were set to PMID: 32898710
Phenotypes for gene: SERPING1 were set to Angioedema, hereditary, 1 and 2 MIM#106100
Review for gene: SERPING1 was set to RED
Added comment: episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts.

Age of onset not typically <5

Treatment Purified C1 inhibitor concentrate (Cinryze, Berinert, HAEGARDA, or Ruconest), Ecallantide (Kalbitor), Icatibant (Firazyr), Lanadelumab, Orladeyo (berotralstat), FFP or solvent-detergent treated plasma, antisense oligonucleotide treatment (donidalorsen)
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SGPL1 Lilian Downie gene: SGPL1 was added
gene: SGPL1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to PMID: 28165343
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 MIM#617575
Review for gene: SGPL1 was set to RED
Added comment: infancy or early childhood with progressive renal dysfunction associated with focal segmental glomerulosclerosis (FSGS), resulting in end-stage renal disease within a few years. Other infants present with primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. Additional features of the disorder can include ichthyosis, acanthosis, adrenal insufficiency, immunodeficiency, and neurologic defects

Rx Hydrocortisone, kidney transplant (treatment doesn't fit screening model as would need to have ESRD before you had it?)
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SLC1A3 Lilian Downie gene: SLC1A3 was added
gene: SLC1A3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A3 were set to PMID: 32754645
Phenotypes for gene: SLC1A3 were set to Episodic ataxia, type 6 MIM#612656
Review for gene: SLC1A3 was set to RED
Added comment: ataxia occurs with febrile illnesses
Episodic attacks lasted 2 to 3 hours and were often associated with nausea, vomiting, photophobia, phonophobia, vertigo, diplopia, and/or slurred speech
Not consistently in children <5 and variable severity

Suggested Rx acetazolamide
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SMARCD2 Lilian Downie gene: SMARCD2 was added
gene: SMARCD2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCD2 were set to PubMed: 28369036, 33279574, 33025377
Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2 MIM#617475
Review for gene: SMARCD2 was set to GREEN
Added comment: recurrent infections due to defective neutrophil development. Bone marrow findings include paucity of neutrophil granulocytes, absence of granule proteins in neutrophils, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. The disorder is apparent from infancy, and patients may die in early childhood unless they undergo hematopoietic stem cell transplantation. Most patients have additional findings, including delayed development, mild dysmorphic features, tooth abnormalities, and distal skeletal defects

Rx bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SNX10 Lilian Downie gene: SNX10 was added
gene: SNX10 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SNX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNX10 were set to PMID: 30885997, PMID: 22499339
Phenotypes for gene: SNX10 were set to Osteopetrosis, autosomal recessive 8 MIM#615085
Review for gene: SNX10 was set to GREEN
Added comment: macrocephaly
failure to thrive
osteopetrosis

Rx bone marrow tranplant
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SOX3 Lilian Downie gene: SOX3 was added
gene: SOX3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SOX3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SOX3 were set to PMID: 31678974, PMID: 15800844
Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked MIM#312000
Review for gene: SOX3 was set to AMBER
Added comment: Amber in our mendeliome - reviewed for ID
Green in pituitary disorders

Xq27.1 duplication most common mechanism - inclusion might be a question of whether we can detect CNV's in this region

neonatal hypoglycemia and growth hormone deficiency in addition to variable deficiencies of other pituitary hormones. Brain hypoplasia of the anterior pituitary with hypoplasia or absence of the lower half of the infundibulum

Rx Growth hormone, levothyroxine, hydrocortisone
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STAT1 Lilian Downie gene: STAT1 was added
gene: STAT1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STAT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STAT1 were set to PMID: 31512162, PMID: 27117246
Phenotypes for gene: STAT1 were set to Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive MIM#613796
Review for gene: STAT1 was set to GREEN
Added comment: combined immunodeficiency
autosomal recessive (AR) complete STAT1 deficiency, AR partial STAT1 deficiency, autosomal dominant (AD) STAT1 deficiency, and AD STAT1 gain-of-function.
gain of function mutations - treat rituxomab
complete - treat BMT
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STIM1 Lilian Downie gene: STIM1 was added
gene: STIM1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STIM1 were set to PMID: 26469693, PMID: 30949876, PMID: 26560041
Phenotypes for gene: STIM1 were set to Immunodeficiency 10 MIM612783
Review for gene: STIM1 was set to GREEN
Added comment: recurrent infections in childhood due to defective T- and NK-cell function, although the severity is variable. Affected individuals may also have hypotonia, hypohidrosis, or dental enamel hypoplasia consistent with amelogenesis imperfecta

Rx bone marrow transpant

Age of onset is consistently <5 but the severity of infections is highly variable - treatment if the phenotype is severe
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STK4 Lilian Downie gene: STK4 was added
gene: STK4 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STK4 were set to PMID: 22294732
Phenotypes for gene: STK4 were set to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM#614868
Review for gene: STK4 was set to GREEN
Added comment: primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect

Rx bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STX16 Lilian Downie gene: STX16 was added
gene: STX16 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STX16 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: STX16 were set to PMID: 33247854, PMID: 34477200, PMID: 29072892
Phenotypes for gene: STX16 were set to Pseudohypoparathyroidism, type IB MIM#603233
Review for gene: STX16 was set to GREEN
Added comment: characterized clinically by isolated renal PTH resistance manifest as hypocalcemia, hyperphosphatemia, and increased serum PTH
without other features of Albright hereditary osteodystrophy
Rx Calcium, calcitriol, levothyroxine, growth hormone
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SYT2 Lilian Downie gene: SYT2 was added
gene: SYT2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYT2 were set to PMID: 32250532, 32776697
Phenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Review for gene: SYT2 was set to GREEN
Added comment: Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.

Only report biallelic for newborn screening ?
monoallelic causes a later onset distal weakness/neuropathy phenotype - still childhood but variable or not clear - not consistently <5yrs
Sources: Expert list
BabyScreen+ newborn screening v0.2063 TBL1X Lilian Downie gene: TBL1X was added
gene: TBL1X was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TBL1X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: TBL1X were set to PMID: 27603907
Phenotypes for gene: TBL1X were set to Hypothyroidism, congenital, nongoitrous, 8 MIM#301033
Review for gene: TBL1X was set to GREEN
Added comment: Small thyroid gland
Detected on newborn screening
Can affect carrier females but more mildly
Association with deafness

Rx thyroxine
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Marked gene: SAR1B as ready
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Gene: sar1b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Classified gene: SAR1B as Green List (high evidence)
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Gene: sar1b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2062 SAR1B Zornitza Stark gene: SAR1B was added
gene: SAR1B was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, gastrointestinal tags were added to gene: SAR1B.
Mode of inheritance for gene: SAR1B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAR1B were set to Chylomicron retention disease, MIM# 246700
Review for gene: SAR1B was set to GREEN
Added comment: Chylomicron retention disease is an autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. Well established gene-disease association.

Congenital onset.

Treatment: low-fat diet with supplementation of fat-soluble vitamins (A, D, E, and K) and oral essential fatty acid supplementation

Non-genetic confirmatory testing: total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol
Sources: Expert list
BabyScreen+ newborn screening v0.2061 SAMD9L Zornitza Stark Marked gene: SAMD9L as ready
BabyScreen+ newborn screening v0.2060 SAMD9L Zornitza Stark gene: SAMD9L was added
gene: SAMD9L was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological, haematological tags were added to gene: SAMD9L.
Mode of inheritance for gene: SAMD9L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD9L were set to 31306780
Phenotypes for gene: SAMD9L were set to Ataxia-pancytopenia syndrome, MIM# 159550
Review for gene: SAMD9L was set to GREEN
Added comment: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.

Ataxia-pancytopenia syndrome (ATXPC) is an autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia. The germline genetic defect is associated with somatic loss of chromosome 7 (monosomy 7) resulting in the deletion of several genes on chromosome 7 that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Expert list
BabyScreen+ newborn screening v0.2059 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
BabyScreen+ newborn screening v0.2058 SAMD9 Zornitza Stark gene: SAMD9 was added
gene: SAMD9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD9 were set to 31306780
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome, MIM# 617053
Review for gene: SAMD9 was set to GREEN
Added comment: MIRAGE syndrome (MIRAGE) is a form of syndromic adrenal hypoplasia, characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. The condition is often fatal within the first decade of life, usually as a result of invasive infection.

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Expert list
BabyScreen+ newborn screening v0.2057 THAP11 Zornitza Stark Marked gene: THAP11 as ready
BabyScreen+ newborn screening v0.2055 TMEM165 Zornitza Stark Marked gene: TMEM165 as ready
BabyScreen+ newborn screening v0.2054 TNFRSF13B Zornitza Stark Marked gene: TNFRSF13B as ready
BabyScreen+ newborn screening v0.2053 TNFAIP3 Zornitza Stark Marked gene: TNFAIP3 as ready
BabyScreen+ newborn screening v0.2052 TMEM165 Lilian Downie gene: TMEM165 was added
gene: TMEM165 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TMEM165 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM165 were set to PMID: 28323990, PMID: 35693943, PMID: 22683087
Phenotypes for gene: TMEM165 were set to Congenital disorder of glycosylation, type IIk MIM#614727
Review for gene: TMEM165 was set to AMBER
Added comment: Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern

Rx D-galactose (single paper, 2 unrelated patients and an in vitro study) ?inadequete evidence for treatment? Might need to check with JC if we would offer it maybe include
Sources: Expert list
BabyScreen+ newborn screening v0.2052 TNFRSF13B Lilian Downie gene: TNFRSF13B was added
gene: TNFRSF13B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFRSF13B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNFRSF13B were set to PMID: 31681716, PMID: 18981294
Phenotypes for gene: TNFRSF13B were set to Immunodeficiency, common variable, 2 MIM#240500
Review for gene: TNFRSF13B was set to RED
Added comment: hypogammaglobulinemia with low serum IgG, IgM, and IgA, and recurrent infections, including otitis media, respiratory tract infections, and gastrointestinal tract infections. Serum IgG and IgA were low, and serum antibody response to immunization with pneumococcal vaccine was decreased, although T cell-dependent response to tetanus toxin was normal.

I think the age of onset is too variable .

Rx immunoglobulin
Sources: Expert list
BabyScreen+ newborn screening v0.2052 TNFAIP3 Lilian Downie gene: TNFAIP3 was added
gene: TNFAIP3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFAIP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNFAIP3 were set to PMID: 31587140, PMID: 33101300
Phenotypes for gene: TNFAIP3 were set to Autoinflammatory syndrome, familial, Behcet-like 1 MIM#616744
Review for gene: TNFAIP3 was set to RED
Added comment: Average age of onset 5yrs - too variable re age of onset.

painful and recurrent mucosal ulceration affecting the oral mucosa, gastrointestinal tract, and genital areas. The onset of symptoms is usually in the first decade, although later onset has been reported. Additional more variable features include skin rash, uveitis, and polyarthritis, consistent with a systemic hyperinflammatory state. Many patients have evidence of autoimmune disease. Rare patients may also have concurrent features of immunodeficiency, including recurrent infections with low numbers of certain white blood cells or impaired function of immune cells.

Treatment: Colchicine, glucocorticoid, mesalazine, cyclosporine, methotrexate, azathioprine, anakinra, rituximab, tocilizumab, infliximab
Sources: Expert list
BabyScreen+ newborn screening v0.2052 RNPC3 Zornitza Stark Marked gene: RNPC3 as ready
BabyScreen+ newborn screening v0.2051 RNPC3 Zornitza Stark gene: RNPC3 was added
gene: RNPC3 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: RNPC3.
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Phenotypes for gene: RNPC3 were set to Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160
Review for gene: RNPC3 was set to GREEN
Added comment: Three unrelated individuals reported with combined and isolated pituitary hormone deficiencies, including GH and TSH.

Onset: congenital.

Treatment: GH, thyroxine.

Non-genetic confirmatory testing: hormone levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2050 RASGRP1 Zornitza Stark Marked gene: RASGRP1 as ready
BabyScreen+ newborn screening v0.2049 RASGRP1 Zornitza Stark gene: RASGRP1 was added
gene: RASGRP1 was added to Baby Screen+ newborn screening. Sources: Literature
treatable, immunological tags were added to gene: RASGRP1.
Mode of inheritance for gene: RASGRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RASGRP1 were set to Immunodeficiency 64 (MIM#618534)
Review for gene: RASGRP1 was set to GREEN
Added comment: Immunodeficiency-64 with lymphoproliferation (IMD64) is an autosomal recessive primary immunodeficiency characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show variably decreased numbers of T cells, with lesser deficiencies of B and NK cells. There is impaired T-cell proliferation and activation; functional defects in B cells and NK cells may also be observed. Patients have increased susceptibility to EBV infection and may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity.

Severe disorder, fatal outcomes reported in childhood.

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Literature
BabyScreen+ newborn screening v0.2048 RAC2 Zornitza Stark Marked gene: RAC2 as ready
BabyScreen+ newborn screening v0.2046 RAC2 Zornitza Stark gene: RAC2 was added
gene: RAC2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: RAC2.
Mode of inheritance for gene: RAC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAC2 were set to Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia MIM# 618986
Review for gene: RAC2 was set to GREEN
Added comment: Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia
13 individuals from 8 unrelated families; mono-allelic; gain of function; multiple mouse models

Mono-allelic missense variants were reported in each individual (5 x De Novo) and resulted in a gain-of -function. (E62K, P34H, N92T, G12R)

These individuals typically presented in infancy with frequent infections, profound leukopaenia, lymphopaenia diarrhoea and hypogammaglobulinaemia.

SCID-like phenotype.

Treatment: IVIG, BMT

Note evidence for the other two immunodeficiency disorders associated with this gene is limited.
Sources: Expert list
BabyScreen+ newborn screening v0.2045 PLS3 Zornitza Stark Marked gene: PLS3 as ready
BabyScreen+ newborn screening v0.2044 PLS3 Zornitza Stark gene: PLS3 was added
gene: PLS3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: PLS3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLS3 were set to 32655496; 25209159; 29736964; 29884797; 28777485; 24088043
Phenotypes for gene: PLS3 were set to Bone mineral density QTL18, osteoporosis - MIM#300910
Review for gene: PLS3 was set to GREEN
Added comment: Females mildly affected: exclude from screening.

Presentation in males similar to OI, though also variable in severity.

Treatment: safe handling techniques, bisphosphonates, pamidronate, zoledronic acid, teriparatide, denosumab, alendronate

Non-genetic confirmatory testing: skeletal survey
Sources: Expert list
BabyScreen+ newborn screening v0.2043 OTULIN Zornitza Stark Marked gene: OTULIN as ready
BabyScreen+ newborn screening v0.2042 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: OTULIN.
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099
Review for gene: OTULIN was set to GREEN
Added comment: Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein (CRP), leukocytosis, and neutrophilia in the absence of any infection.

Onset is generally in infancy.

Treatment: inflixiimab, anakinra, etanercept, corticosteroids.

Non-genetic confirmatory testing: no.
Sources: Expert list
BabyScreen+ newborn screening v0.2041 OAS1 Zornitza Stark Marked gene: OAS1 as ready
BabyScreen+ newborn screening v0.2040 OAS1 Zornitza Stark gene: OAS1 was added
gene: OAS1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: OAS1.
Mode of inheritance for gene: OAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OAS1 were set to 34145065; 29455859
Phenotypes for gene: OAS1 were set to Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042
Review for gene: OAS1 was set to GREEN
Added comment: Immunodeficiency-100 with pulmonary alveolar proteinosis and hypogammaglobulinemia (IMD100) is primarily a lung disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis (PAP) in the first months of life. Affected individuals may have normal respiratory function at birth. Development of the disorder appears to be influenced or triggered by viral infection, manifest as progressive respiratory insufficiency, confluent consolidations on lung imaging, and diffuse collection of periodic acid-Schiff (PAS)-positive material in pulmonary alveoli associated with small and nonfoamy alveolar macrophages. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly. Many patients die of respiratory failure in infancy or early childhood.

Treatment: IVIG; BMT is curative.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2039 NFKBIA Zornitza Stark Marked gene: NFKBIA as ready
BabyScreen+ newborn screening v0.2038 NFKBIA Zornitza Stark gene: NFKBIA was added
gene: NFKBIA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: NFKBIA.
Mode of inheritance for gene: NFKBIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NFKBIA were set to Ectodermal dysplasia and immunodeficiency 2 MIM# 612132
Review for gene: NFKBIA was set to GREEN
Added comment: 12 heterozygous variants were identified in 15 unrelated individuals (de novo in 14 individuals and somatic mosaicism in 1 individual).

Functional studies & two mouse models; demonstrate reported NFKBIA gain-of-function variants resulting in impaired NFKB1 activity.

The majority of individuals displayed recurrent infections, chronic diarrhoea, agammaglobulinaemia, increased IgM, and defects in teeth (hair, nail, sweat glands).

Onset is generally in infancy.

Treatment: BMT.

Non-genetic confirmatory testing: no
Sources: Expert list
BabyScreen+ newborn screening v0.2037 NAXE Zornitza Stark Marked gene: NAXE as ready
BabyScreen+ newborn screening v0.2037 NAXE Zornitza Stark gene: NAXE was added
gene: NAXE was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: NAXE.
Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXE were set to 27122014; 27616477; 31758406
Phenotypes for gene: NAXE were set to Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186
Review for gene: NAXE was set to RED
Added comment: Early-onset progressive encephalopathy with brain oedema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported.

Treatment: niacin

However, single case reported. Treatment not established.
Sources: Expert list
BabyScreen+ newborn screening v0.2036 NAXD Zornitza Stark Marked gene: NAXD as ready
BabyScreen+ newborn screening v0.2035 NAXD Zornitza Stark gene: NAXD was added
gene: NAXD was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: NAXD.
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 30576410; 31755961; 32462209; 35231119
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321
Review for gene: NAXD was set to AMBER
Added comment: Seven unrelated cases, episodes of fever/infection prior to deterioration reported. Variable phenotype: one patient reported with neurodevelopmental disorder, autism spectrum disorder and a muscular-dystrophy-like myopathy; another with progressive encephalopathy with brain oedema. Patient cells and muscle biopsies also showed impaired mitochondrial function, higher sensitivity to metabolic stress, and decreased mitochondrial reactive oxygen species production. In vitro functional assays also conducted.

Treatment: niacin

However, only two cases reported. Treatment not established.
Sources: Expert list
BabyScreen+ newborn screening v0.2034 MYD88 Zornitza Stark Marked gene: MYD88 as ready
BabyScreen+ newborn screening v0.2033 MYD88 Zornitza Stark gene: MYD88 was added
gene: MYD88 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MYD88.
Mode of inheritance for gene: MYD88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYD88 were set to 18669862; 20538326; 31301515
Phenotypes for gene: MYD88 were set to Immunodeficiency 68, MIM# 612260
Review for gene: MYD88 was set to GREEN
Added comment: Immunodeficiency-68 (IMD68) is an autosomal recessive primary immunodeficiency characterized by severe systemic and invasive bacterial infections beginning in infancy or early childhood. The most common organisms implicated are Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas, although other organisms may be observed.

At least 7 families and a mouse model.

Treatment: Prophylactic antibiotic treatment, pneumococcal, meningococcal, haemophilus influenzae vaccines, and immunoglobulin replacement.

Non-genetic confirmatory testing: toll-like receptor function
Sources: Expert list
BabyScreen+ newborn screening v0.2032 MTHFS Zornitza Stark Marked gene: MTHFS as ready
BabyScreen+ newborn screening v0.2032 MTHFS Zornitza Stark gene: MTHFS was added
gene: MTHFS was added to Baby Screen+ newborn screening. Sources: Expert list
metabolic tags were added to gene: MTHFS.
Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFS were set to 30031689; 31844630; 22303332
Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367
Review for gene: MTHFS was set to RED
Added comment: Established gene-disease association.

Onset in infancy. Severe disorder.

Treatment: single report of some improvement with combination of oral L-5- methyltetrahydrofolate and intramuscular methylcobalamin
Sources: Expert list
BabyScreen+ newborn screening v0.2031 MTHFD1 Zornitza Stark Marked gene: MTHFD1 as ready
BabyScreen+ newborn screening v0.2030 MTHFD1 Zornitza Stark gene: MTHFD1 was added
gene: MTHFD1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological, haematological tags were added to gene: MTHFD1.
Mode of inheritance for gene: MTHFD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFD1 were set to 32414565; 19033438
Phenotypes for gene: MTHFD1 were set to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780
Review for gene: MTHFD1 was set to GREEN
Added comment: 8 individuals from 4 unrelated families have been reported; multiple mouse models

7 individuals were Compound heterozygous (nonsense & missense) and 1 was homozygous (missense) for MTHFD1 variants often resulting in alteration of highly conserved residues in binding-sites.

Individuals typically present with megaloblastic anaemia, atypical hemolytic uremic syndrome, hyperhomocysteinaemia, microangiopathy, recurrent infections and autoimmune diseases.

Treatment: hydroxocobalamin, folinic acid and betaine

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile, complete blood count with MCV, plasma homocysteine and methylmalonic acid levels, CSF
Sources: Expert list
BabyScreen+ newborn screening v0.2029 MNX1 Zornitza Stark Marked gene: MNX1 as ready
BabyScreen+ newborn screening v0.2027 MALT1 Zornitza Stark Marked gene: MALT1 as ready
BabyScreen+ newborn screening v0.2026 MALT1 Zornitza Stark gene: MALT1 was added
gene: MALT1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MALT1.
Mode of inheritance for gene: MALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MALT1 were set to Immunodeficiency 12 MIM# 615468
Review for gene: MALT1 was set to GREEN
Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency.

Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains.

All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.

Treatment: prophylactic antibiotics, IVIG, BMT.

Non-genetic confirmatory testing: no
Sources: Expert list
BabyScreen+ newborn screening v0.2025 MAGT1 Zornitza Stark Marked gene: MAGT1 as ready
BabyScreen+ newborn screening v0.2024 MAGT1 Zornitza Stark gene: MAGT1 was added
gene: MAGT1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MAGT1.
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 31036665; 31714901
Phenotypes for gene: MAGT1 were set to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853)
Review for gene: MAGT1 was set to GREEN
Added comment: XMEN is an X-linked recessive immunodeficiency characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. Affected individuals have chronic Epstein-Barr virus (EBV) infection and are susceptible to the development of EBV-associated B-cell lymphoproliferative disorders.

Variable age of onset, including in early childhood.

Treatment: Mg supplementation; IVIG, BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile, Carbohydrate deficient glycosylation profile
Sources: Expert list
BabyScreen+ newborn screening v0.2023 LRBA Zornitza Stark Marked gene: LRBA as ready
BabyScreen+ newborn screening v0.2022 LRBA Zornitza Stark gene: LRBA was added
gene: LRBA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: LRBA.
Mode of inheritance for gene: LRBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRBA were set to 22608502; 22721650; 25468195; 26206937; 33155142; 31887391
Phenotypes for gene: LRBA were set to Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700
Review for gene: LRBA was set to GREEN
Added comment: Well established gene-disease association.

Generally childhood onset with recurrent infections and autoimmune phenomena.

Treatment: abatacept, BMT.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2021 LIG1 Zornitza Stark Marked gene: LIG1 as ready
BabyScreen+ newborn screening v0.2020 LIG1 Zornitza Stark gene: LIG1 was added
gene: LIG1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: LIG1.
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to 30395541
Phenotypes for gene: LIG1 were set to Immunodeficiency 96, MIM# 619774
Review for gene: LIG1 was set to GREEN
Added comment: Established gene-disease association.

Onset is generally in early childhood.

Presents with recurrent severe infections.

Treatment: IVIG, BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile, complete blood count
Sources: Expert list
BabyScreen+ newborn screening v0.2019 LEP Zornitza Stark Marked gene: LEP as ready
BabyScreen+ newborn screening v0.2018 LEP Zornitza Stark gene: LEP was added
gene: LEP was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: LEP.
Mode of inheritance for gene: LEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LEP were set to 26567097
Phenotypes for gene: LEP were set to Obesity, morbid, due to leptin deficiency (MIM#614962)
Review for gene: LEP was set to GREEN
Added comment: Established gene-disease association.

Onset is in infancy/early childhood. Similar disorders included.

Treatment: metreleptin.

Non-genetic confirmatory testing: leptin level.
Sources: Expert list
BabyScreen+ newborn screening v0.2017 JAGN1 Zornitza Stark Marked gene: JAGN1 as ready
BabyScreen+ newborn screening v0.2016 JAGN1 Zornitza Stark gene: JAGN1 was added
gene: JAGN1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: JAGN1.
Mode of inheritance for gene: JAGN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAGN1 were set to 25129144
Phenotypes for gene: JAGN1 were set to Neutropenia, severe congenital, 6, autosomal recessive, MIM# 616022
Review for gene: JAGN1 was set to GREEN
Added comment: Established gene-disease association.

Typically presents in early childhood with severe infections.

Treatment: G-CSF, BMT.

Non-genetic confirmatory testing: complete blood count, bone marrow aspiration and biopsy
Sources: Expert list
BabyScreen+ newborn screening v0.2015 TNFRSF13C Zornitza Stark Marked gene: TNFRSF13C as ready
BabyScreen+ newborn screening v0.2014 ITK Zornitza Stark Marked gene: ITK as ready
BabyScreen+ newborn screening v0.2013 ITK Zornitza Stark gene: ITK was added
gene: ITK was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: ITK.
Mode of inheritance for gene: ITK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITK were set to Lymphoproliferative syndrome 1, MIM# 613011
Review for gene: ITK was set to GREEN
Added comment: 7 individuals from 5 unrelated families reported homozygous (missense/ nonsense) ITK variants consistent with Lymphoproliferative syndrome phenotype. Triggered by EBV infection.

Two ITK-deficient mouse models demonstrated reduced T cells (CD4+), causing decreased CD4 to CD8 ratio.

Patients displayed early onset of features typically including fever, lymphadenopathy, autoimmune disorders, low immunoglobulins and high EBV viral load.

Fatal without BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile.
Sources: Expert list
BabyScreen+ newborn screening v0.2012 IRS4 Zornitza Stark changed review comment from: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported.

Most identified through standard NBS.
Sources: Expert list; to: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported.

Most identified through standard NBS.

Treatment: thyroxine.
Sources: Expert list
BabyScreen+ newborn screening v0.2012 IRS4 Zornitza Stark Marked gene: IRS4 as ready
BabyScreen+ newborn screening v0.2011 IRS4 Zornitza Stark gene: IRS4 was added
gene: IRS4 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: IRS4.
Mode of inheritance for gene: IRS4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRS4 were set to 30061370
Phenotypes for gene: IRS4 were set to Hypothyroidism, congenital, nongoitrous, 9, MIM# 301035
Review for gene: IRS4 was set to GREEN
Added comment: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported.

Most identified through standard NBS.
Sources: Expert list
BabyScreen+ newborn screening v0.2010 TNFRSF13C Lilian Downie gene: TNFRSF13C was added
gene: TNFRSF13C was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFRSF13C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF13C were set to PMID: 19666484, PMID: 27250108, PMID: 18025937
Phenotypes for gene: TNFRSF13C were set to Immunodeficiency, common variable, 4 MIM#613494
Review for gene: TNFRSF13C was set to RED
Added comment: Amber in our mendeliome
Later childhood or adult onset.
BAFFR deficiency in humans is characterized by very few circulating B cells, very low IgM and IgG serum concentrations but normal or high IgA levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2010 IL36RN Zornitza Stark Marked gene: IL36RN as ready
BabyScreen+ newborn screening v0.2009 IL36RN Zornitza Stark gene: IL36RN was added
gene: IL36RN was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL36RN.
Mode of inheritance for gene: IL36RN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL36RN were set to 31286990
Phenotypes for gene: IL36RN were set to Psoriasis 14, pustular, MIM# 614204
Review for gene: IL36RN was set to GREEN
Added comment: Generalized pustular psoriasis (GPP) is a life-threatening disease characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein.

Variable age of onset but predominantly in infancy/early childhood.

Treatment: ustekinumab, secukinumab, etanercept.
Sources: Expert list
BabyScreen+ newborn screening v0.2008 IL2RA Zornitza Stark Marked gene: IL2RA as ready
BabyScreen+ newborn screening v0.2007 IL2RA Zornitza Stark gene: IL2RA was added
gene: IL2RA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL2RA.
Mode of inheritance for gene: IL2RA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL2RA were set to Immunodeficiency 41 with lymphoproliferation and autoimmunity, MIM# 606367
Review for gene: IL2RA was set to GREEN
Added comment: Immunodeficiency-41 is a disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation.

At least 4 unrelated families reported.

Treatment: rapamycin, bone marrow transplant.

Confirmatory non-genetic testing: flow cytometric analysis.
Sources: Expert list
BabyScreen+ newborn screening v0.2006 IL21R Zornitza Stark Marked gene: IL21R as ready
BabyScreen+ newborn screening v0.2005 IL21R Zornitza Stark gene: IL21R was added
gene: IL21R was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL21R.
Mode of inheritance for gene: IL21R was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL21R were set to Immunodeficiency 56, MIM# 615207
Review for gene: IL21R was set to GREEN
Added comment: Biallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections.

More than 20 individuals reported. Recent series of 13 individuals: the main clinical manifestations were recurrent bacterial (84.6%), fungal (46.2%), and viral (38.5%) infections; cryptosporidiosis-associated cholangitis (46.2%); and asthma (23.1%). Inflammatory skin diseases (15.3%) and recurrent anaphylaxis (7.9%) constitute novel phenotypes of this combined immunodeficiency. Most patients exhibited hypogammaglobulinaemia and reduced proportions of memory B cells, circulating T follicular helper cells, MAIT cells and terminally differentiated NK cells. However, IgE levels were elevated in 50% of IL-21R-deficient patients.

Onset: infancy/early childhood.

Treatment: BMT.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2004 IL1RN Zornitza Stark Marked gene: IL1RN as ready
BabyScreen+ newborn screening v0.2002 IKZF1 Zornitza Stark Marked gene: IKZF1 as ready
BabyScreen+ newborn screening v0.2001 IKZF1 Zornitza Stark gene: IKZF1 was added
gene: IKZF1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IKZF1 were set to Immunodeficiency, common variable, 13 MIM# 616873
Added comment: Over 25 individuals from 9 unrelated families with variants in IKZF1 displaying Immunodeficiency; three mouse models Heterozygous missense, frameshift and deletion variants in IKZF1 gene resulting in loss or alteration of a zinc finger DNA contact site cause LoF. Typically presents with recurrent bacterial respiratory infections, hypogammaglobulinaemia and low Ig levels; variable age of onset.

PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.

Included primarily for LoF phenotype.

Treatment: IVIG and BMT.

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.2000 IKBKB Zornitza Stark changed review comment from: Primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinaemia with relatively normal numbers of B and T cells.

Treatment: bone marrow transplant.
Sources: Expert list; to: Primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinaemia with relatively normal numbers of B and T cells.

Treatment: bone marrow transplant.

Limited evidence for mono-allelic disease.
Sources: Expert list
BabyScreen+ newborn screening v0.2000 IKBKB Zornitza Stark Marked gene: IKBKB as ready
BabyScreen+ newborn screening v0.1999 IKBKB Zornitza Stark gene: IKBKB was added
gene: IKBKB was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IKBKB.
Mode of inheritance for gene: IKBKB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IKBKB were set to Immunodeficiency 15B, MIM# 615592
Review for gene: IKBKB was set to GREEN
Added comment: Primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinaemia with relatively normal numbers of B and T cells.

Treatment: bone marrow transplant.
Sources: Expert list
BabyScreen+ newborn screening v0.1998 IFNGR2 Zornitza Stark Marked gene: IFNGR2 as ready
BabyScreen+ newborn screening v0.1997 IFNGR2 Zornitza Stark gene: IFNGR2 was added
gene: IFNGR2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IFNGR2.
Mode of inheritance for gene: IFNGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFNGR2 were set to Immunodeficiency 28, mycobacteriosis, MIM# 614889
Review for gene: IFNGR2 was set to AMBER
Added comment: At least 5 unrelated families reported.

Commonest trigger is BCG vaccination, which is not part of the routine schedule in Australia, therefore exclude.

Treatment: BMT; avoidance of BCG.
Sources: Expert list
BabyScreen+ newborn screening v0.1996 IFNGR1 Zornitza Stark Marked gene: IFNGR1 as ready
BabyScreen+ newborn screening v0.1995 IFNGR1 Zornitza Stark gene: IFNGR1 was added
gene: IFNGR1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IFNGR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IFNGR1 were set to Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950; Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978
Review for gene: IFNGR1 was set to AMBER
Added comment: Variable age of onset. Most common precipitant is BCG vaccination, which is not part of the routine schedule in Australia, therefore exclude.

Treatment: BMT; avoidance of BCG.
Sources: Expert list
BabyScreen+ newborn screening v0.1994 IFITM5 Zornitza Stark Marked gene: IFITM5 as ready
BabyScreen+ newborn screening v0.1993 IFITM5 Zornitza Stark gene: IFITM5 was added
gene: IFITM5 was added to Baby Screen+ newborn screening. Sources: Expert list
5'UTR, treatable, skeletal tags were added to gene: IFITM5.
Mode of inheritance for gene: IFITM5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFITM5 were set to 22863190; 22863195; 32383316; 24519609
Phenotypes for gene: IFITM5 were set to Osteogenesis imperfecta, type V MIM#610967
Review for gene: IFITM5 was set to GREEN
Added comment: A recurrent c.-14C>T variant has been reported in many patients with type V OI. It introduces an alternative in-frame start codon upstream that is stronger than the reference start codon in transfected HEK cells (PMIDs: 22863190, 22863195). However, the effect of mutant protein (5 amino acids longer) remains unknown but neomorphic mechanism is a widely accepted hypothesis (PMIDs: 25251575, 32383316).

Variable severity, including within families. However, severe perinatal presentations reported.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.1992 ICOS Zornitza Stark Marked gene: ICOS as ready
BabyScreen+ newborn screening v0.1991 ICOS Zornitza Stark gene: ICOS was added
gene: ICOS was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: ICOS.
Mode of inheritance for gene: ICOS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ICOS were set to Immunodeficiency, common variable, 1 MIM# 607594
Review for gene: ICOS was set to GREEN
Added comment: 15 affected individuals from 8 unrelated families reported with ICOS variants and displayed immunodeficiency, common variable, 1 phenotype; three mouse models.

Homozygous and compound heterozygous deletion and missense variants, with the most frequent variant being a 442 nucleotide deletion.

Patients typically presented with recurrent bacterial respiratory & gastrointestinal infections and low IgG/IgA.

Congenital onset.

Treatment: replacement immunoglobulin treatment, bone marrow transplant.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Marked gene: IARS as ready
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Gene: iars has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Classified gene: IARS as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Gene: iars has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1989 IARS Zornitza Stark Tag treatable tag was added to gene: IARS.
Tag metabolic tag was added to gene: IARS.
BabyScreen+ newborn screening v0.1989 IARS Zornitza Stark gene: IARS was added
gene: IARS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735; 34194004
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093
Review for gene: IARS was set to AMBER
Added comment: Established gene-disease association.

Congenital, multi-system metabolic disorder.

N=1 study of Isoleucine supplementation and protein fortification (2.5mg/kg/day, during illness 3.5 g/kg/day) with some clinical improvement.
Sources: Expert list
BabyScreen+ newborn screening v0.1988 TNFRSF1A Zornitza Stark Marked gene: TNFRSF1A as ready
BabyScreen+ newborn screening v0.1987 TOP2B Zornitza Stark Marked gene: TOP2B as ready
BabyScreen+ newborn screening v0.1986 TPK1 Zornitza Stark Marked gene: TPK1 as ready
BabyScreen+ newborn screening v0.1985 TRNT1 Zornitza Stark Marked gene: TRNT1 as ready
BabyScreen+ newborn screening v0.1984 TRPM6 Zornitza Stark Marked gene: TRPM6 as ready
BabyScreen+ newborn screening v0.1983 UCP2 Zornitza Stark Marked gene: UCP2 as ready
BabyScreen+ newborn screening v0.1982 TNFRSF1A Lilian Downie gene: TNFRSF1A was added
gene: TNFRSF1A was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFRSF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNFRSF1A were set to PMID: 11175303, PMID: 32066461, PMID: 29773275, PMID: 32831641
Phenotypes for gene: TNFRSF1A were set to Periodic fever, familial MIM#142680
Penetrance for gene: TNFRSF1A were set to Incomplete
Review for gene: TNFRSF1A was set to RED
Added comment: Strong gene disease association
Childhood onset but age not consistently under 5 and cases of adult onset
reports of variable penetrance
Rx
NSAIDs, corticosteroids, Etanercept , anakinra, canakinumab, tocilizumab

because there is no non-molecular confirmatory test I think should be red for variability of age of onset and severity of symptoms.
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TOP2B Lilian Downie gene: TOP2B was added
gene: TOP2B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOP2B were set to PMID: 31409799, PMID: 35063500, PMID: 32128574, PMID: 33459963
Phenotypes for gene: TOP2B were set to B-cell immunodeficiency, distal limb anomalies, and urogenital malformations MIM#609296
Review for gene: TOP2B was set to AMBER
Added comment: congenital onset
humoral immunodeficiency with undetectable B cells, distal limb anomalies, dysmorphic facial features, and urogenital malformations

Treatment immunoglobulin (only partially treats phenotype) no literature for evidence around immunoglobulin treatment.

Suggest RED but maybe discuss with immunologist?
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TPK1 Lilian Downie gene: TPK1 was added
gene: TPK1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPK1 were set to PMID: 33086386, 32679198, 22152682, PMID: 33231275
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458
Review for gene: TPK1 was set to GREEN
Added comment: Strong gene disease association
Variable age of onset but always under 5years

Thiamine metabolism dysfunction syndrome-5 (THMD5) is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (Mayr et al., 2011).

Biotin and thiamine therapy - newer evidence (2021) suggests early thiamine therapy may prevent any neurologic deficits.
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TRNT1 Lilian Downie gene: TRNT1 was added
gene: TRNT1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRNT1 were set to PMID: 25193871, PMID: 23553769, PMID: 33936027, PMID: 26494905
Phenotypes for gene: TRNT1 were set to Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay MIM#616084
Review for gene: TRNT1 was set to AMBER
Added comment: Onset infancy
Strong gene disease association

Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndromic disorder characterized by onset of severe sideroblastic anemia in the neonatal period or infancy. Affected individuals show delayed psychomotor development with variable neurodegeneration. Recurrent periodic fevers without an infectious etiology occur throughout infancy and childhood; immunologic work-up shows B-cell lymphopenia and hypogammaglobulinemia. Other more variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy. Death in the first decade may occur (summary by Wiseman et al., 2013).

Bone marrow transplant (hematopoietic stem cell transplantation (HSCT)), replacement immunoglobulin treatment

Allelic disease: Retinitis pigmentosa and erythrocytic microcytosis MIM#616959. Also AR.
DeLuca et al. (2016) concluded that hypomorphic TRNT1 mutations can cause a recessive disease that is almost entirely limited to the retina - this has teenage onset and is not treatable. can we exclude these variants?
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TRPM6 Lilian Downie gene: TRPM6 was added
gene: TRPM6 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to PMID: 35903165, PMID: 18818955
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal MIM#602014
Review for gene: TRPM6 was set to GREEN
Added comment: Hypomagnaesemia and hypocalcaemia
Hypocalcemia is a secondary consequence of parathyroid failure and parathyroid hormone resistance as a result of severe magnesium deficiency. The disease typically manifests during the first months of life with generalized convulsions or signs of increased neuromuscular excitability, such as muscle spasms or tetany. Untreated, the disease may be fatal or lead to severe neurologic damage. Treatment includes immediate administration of magnesium, usually intravenously, followed by life-long high-dose oral magnesium (review by Knoers, 2009).
Sources: Expert list
BabyScreen+ newborn screening v0.1982 UNG Zornitza Stark Marked gene: UNG as ready
BabyScreen+ newborn screening v0.1981 UMPS Zornitza Stark Marked gene: UMPS as ready
BabyScreen+ newborn screening v0.1980 NLGN4X Zornitza Stark Marked gene: NLGN4X as ready
BabyScreen+ newborn screening v0.1978 HSD11B2 Zornitza Stark Marked gene: HSD11B2 as ready
BabyScreen+ newborn screening v0.1977 HSD11B2 Zornitza Stark gene: HSD11B2 was added
gene: HSD11B2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: HSD11B2.
Mode of inheritance for gene: HSD11B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HSD11B2 were set to Apparent mineralocorticoid excess, MIM# 218030; MONDO:0009025
Review for gene: HSD11B2 was set to GREEN
Added comment: Apparent mineralocorticoid excess (AME) is an autosomal recessive form of low-renin hypertension associated with low aldosterone, metabolic alkalosis, hypernatremia, and hypokalemia. The disorder is due to a congenital defect in 11-beta-hydroxysteroid dehydrogenase type II (HSD11B2) activity, resulting in decreased conversion of biologically active cortisol to inactive cortisone; this defect allows cortisol to act as a ligand for the mineralocorticoid receptor, resulting in sodium retention and volume expansion. There is a favorable therapeutic response to spironolactone. More than 10 unrelated families reported.

Onset is usually in infancy or early childhood.

Non-genetic confirmatory testing: aldosterone, renin, potassium levels
Sources: Expert list
BabyScreen+ newborn screening v0.1976 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
BabyScreen+ newborn screening v0.1975 HOGA1 Zornitza Stark gene: HOGA1 was added
gene: HOGA1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: HOGA1.
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 20797690; 21896830; 22391140
Phenotypes for gene: HOGA1 were set to Hyperoxaluria, primary, type III MIM#613616
Review for gene: HOGA1 was set to GREEN
Added comment: Well-established association with primary hyperoxaluria type III. c.700+5G>T is a recurrent pathogenic variant in European populations (possibly founder) and has high frequency in gnomad (0.2-0.3%).

Onset in infancy, progressive multi-system disorder.

Treatment: pyridoxine, drinking large volumes, alkalinzation of urine, pyrophosphate-containing solutions, liver-kidney transplant

Non-genetic confirmatory testing: urinary oxalate
Sources: Expert list
BabyScreen+ newborn screening v0.1974 UMPS Lilian Downie changed review comment from: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list; to: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Better check with John who wrote the paper!! PMID: 25030255

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list
BabyScreen+ newborn screening v0.1974 UMPS Lilian Downie gene: UMPS was added
gene: UMPS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: UMPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UMPS were set to PMID: 9042911, PMID: 28205048, PMID: 25757096, PMID: 33489760
Phenotypes for gene: UMPS were set to Orotic aciduria MIM#258900
Review for gene: UMPS was set to GREEN
Added comment: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list
BabyScreen+ newborn screening v0.1974 UNG Lilian Downie gene: UNG was added
gene: UNG was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: UNG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNG were set to PubMed: 12958596, PMID: 15967827, PMID: 19202054, PMID: 16860315
Phenotypes for gene: UNG were set to Immunodeficiency with hyper IgM, type 5 MIM#608106
Review for gene: UNG was set to RED
Added comment: normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations.
susceptibility to bacterial infections, lymphoid hyperplasia
only 3 patients reported in a single paper ?
Rx immunoglobulin replacement according to Rx genes but I can't find actual papers - i don't think there is enough evidence regarding age of onset or treatability.
Sources: Expert list
BabyScreen+ newborn screening v0.1974 HELLS Zornitza Stark Marked gene: HELLS as ready
BabyScreen+ newborn screening v0.1973 HELLS Zornitza Stark gene: HELLS was added
gene: HELLS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: HELLS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 4, MIM# 616911
Review for gene: HELLS was set to GREEN
Added comment: Congenital onset.

Immunodeficiency-centromeric instability-facial anomalies syndrome-4 is characterized by recurrent infections in childhood and variable dysmorphic facial features. Laboratory studies show hypomethylation of certain chromosomal regions. Additional features, including delayed development, are variable. At least 4 unrelated families reported.

Treatment: bone marrow transplant.
Sources: Expert list
BabyScreen+ newborn screening v0.1972 USP18 Zornitza Stark Marked gene: USP18 as ready
BabyScreen+ newborn screening v0.1971 VKORC1 Zornitza Stark Marked gene: VKORC1 as ready
BabyScreen+ newborn screening v0.1969 WDR1 Zornitza Stark Marked gene: WDR1 as ready
BabyScreen+ newborn screening v0.1968 GPIHBP1 Zornitza Stark Marked gene: GPIHBP1 as ready
BabyScreen+ newborn screening v0.1967 GPIHBP1 Zornitza Stark gene: GPIHBP1 was added
gene: GPIHBP1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GPIHBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPIHBP1 were set to 31390500
Phenotypes for gene: GPIHBP1 were set to Hyperlipoproteinemia, type 1D MIM#615947; familial chylomicronemia syndrome
Review for gene: GPIHBP1 was set to GREEN
Added comment: Well-established gene-disease association.

Usually presents in childhood with episodes of abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly.

Approximately 25% of affected children develop symptoms before age one year and the majority develop symptoms before age ten years; however, some individuals present for the first time during pregnancy.

Treatment: volanesorsen, dietary fat restriction

Non-genetic confirmatory testing: triglyceride level
Sources: Expert list
BabyScreen+ newborn screening v0.1966 GHRHR Zornitza Stark Marked gene: GHRHR as ready
BabyScreen+ newborn screening v0.1965 GHRHR Zornitza Stark gene: GHRHR was added
gene: GHRHR was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GHRHR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GHRHR were set to 8528260; 10084571; 11232012
Phenotypes for gene: GHRHR were set to Growth hormone deficiency, isolated, type IV, MIM# 618157
Review for gene: GHRHR was set to GREEN
Added comment: IGHD type IV is characterized by early and severe growth failure (height SDS up to -7.4), a blunted growth hormone (GH) response to different provocation tests and low insulin-like growth factor-I and IGF-binding protein-3 concentrations, and a good response to growth hormone treatment. At least three unrelated families reported.

Non-genetic confirmatory testing: growth hormone stimulation test
Sources: Expert list
BabyScreen+ newborn screening v0.1964 GHR Zornitza Stark Marked gene: GHR as ready
BabyScreen+ newborn screening v0.1963 GHR Zornitza Stark gene: GHR was added
gene: GHR was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GHR were set to Growth hormone insensitivity, partial, MIM# 604271; Laron dwarfism, MIM# 262500
Review for gene: GHR was set to GREEN
Added comment: Well established gene-disease association.

Congenital onset.

Treatment: growth hormone.

Non-genetic confirmatory testing: growth hormone stimulation test
Sources: Expert list
BabyScreen+ newborn screening v0.1962 GH1 Zornitza Stark Marked gene: GH1 as ready
BabyScreen+ newborn screening v0.1961 GH1 Zornitza Stark gene: GH1 was added
gene: GH1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GH1 were set to Growth hormone deficiency, isolated, type IA, MIM# 262400; Growth hormone deficiency, isolated, type II, MIM# 173100; Kowarski syndrome, MIM# 262650
Review for gene: GH1 was set to GREEN
Added comment: Well established gene-disease association. Congenital onset.

Treatment: growth hormone.

Non-genetic confirmatory test: growth hormone stimulation test
Sources: Expert list
BabyScreen+ newborn screening v0.1960 GFI1 Zornitza Stark Marked gene: GFI1 as ready
BabyScreen+ newborn screening v0.1959 GFI1 Zornitza Stark gene: GFI1 was added
gene: GFI1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GFI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GFI1 were set to 12778173; 20560965; 11810106; 22684987
Phenotypes for gene: GFI1 were set to Neutropenia, severe congenital 2, autosomal dominant, MIM# 613107
Review for gene: GFI1 was set to GREEN
Added comment: At least three unrelated families reported, and supportive functional data.

Severe congenital immunodeficiency.

Treatment: granulocyte colony-stimulating factor (G-CSF), Bone marrow transplant

Non-genetic confirmatory testing: FBE.
Sources: Expert list
BabyScreen+ newborn screening v0.1958 VKORC1 Lilian Downie gene: VKORC1 was added
gene: VKORC1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: VKORC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: VKORC1 were set to PMID:14765194, PMID: 26287237
Phenotypes for gene: VKORC1 were set to Vitamin K-dependent clotting factors, combined deficiency of, 2 MIM#607473
Review for gene: VKORC1 was set to AMBER
Added comment: Risk of intracranial haemmorhage in first weeks of life
Treatable with vitamin K
See below summary - feels like should be green for that homozygous mutation but not sure how to manage the gene overall? not report other variants?
Monoallelic - warfarin resistance

There is only one mutation known to result in the VKCFD2 phenotype. VKORC1:p.Arg98Trp causes diminished vitamin K epoxide reductase (VKOR) activity compared to that of the wild-type enzyme [15]. VKCFD2 patients exhibit severely diminished activities for the VKD coagulation factors and suffer spontaneous or surgery/injury induced bleeding episodes [16,17]. In addition to this haemorrhagic phenotype, abnormalities in epiphyseal growth have been reported in one case [18]. This phenotype is very rare. Worldwide, there are only four unrelated families known to be affected with VKCFD2 [16,17,18].
Sources: Expert list
BabyScreen+ newborn screening v0.1958 WDR1 Lilian Downie gene: WDR1 was added
gene: WDR1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WDR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR1 were set to PMID: 32960541, 27994071, 27557945
Phenotypes for gene: WDR1 were set to Periodic fever, immunodeficiency, and thrombocytopenia syndrome MIM#150550
Review for gene: WDR1 was set to GREEN
Added comment: Strong gene disease association
Phenotype is early onset immunodeficiency with infections ++ and severe stomatitis
Treatable with bone marrow transplant.
Sources: Expert list
BabyScreen+ newborn screening v0.1958 WDR72 Zornitza Stark Marked gene: WDR72 as ready
BabyScreen+ newborn screening v0.1958 WDR72 Zornitza Stark Phenotypes for gene: WDR72 were changed from Distal renal tubular acidosis to Amelogenesis imperfecta, type IIA3, MIM# 613211; Distal RTA MONDO:0015827
BabyScreen+ newborn screening v0.1956 WIPF1 Zornitza Stark Marked gene: WIPF1 as ready
BabyScreen+ newborn screening v0.1955 WNK4 Zornitza Stark Marked gene: WNK4 as ready
BabyScreen+ newborn screening v0.1954 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
BabyScreen+ newborn screening v0.1953 ZNF143 Zornitza Stark Marked gene: ZNF143 as ready
BabyScreen+ newborn screening v0.1952 WDR72 Lilian Downie gene: WDR72 was added
gene: WDR72 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WDR72 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR72 were set to PMID: 30028003, PMID: 30779877, PMID:36836560, PMID: 33033857
Phenotypes for gene: WDR72 were set to Distal renal tubular acidosis
Review for gene: WDR72 was set to GREEN
Added comment: Amelogenesis imperecta - thickened and disoloured dental enamal with RTA
Reduced penetrance or variable expression? Some patients only have the tooth phenotype...
Presents with polyuria and growth restriction
Treat with oral alkali replacement therapy, potassium chloride
Sources: Expert list
BabyScreen+ newborn screening v0.1952 WIPF1 Lilian Downie gene: WIPF1 was added
gene: WIPF1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WIPF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WIPF1 were set to PMID: 27742395, PMID: 30450104, PMID: 22231303
Phenotypes for gene: WIPF1 were set to Wiskott-Aldrich syndrome 2 MIM#614493
Review for gene: WIPF1 was set to GREEN
Added comment: Infant onset
recurrent infections, thrombycytopenia and eczema
Immunology testing to correlate
Treatment/cure with bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.1952 WNK4 Lilian Downie gene: WNK4 was added
gene: WNK4 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WNK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WNK4 were set to PMID: 22073419, PMID: 31795491, PMID: 10869238,
Phenotypes for gene: WNK4 were set to Pseudohypoaldosteronism, type IIB MIM#614491
Review for gene: WNK4 was set to GREEN
Added comment: Hyperkalaemia and hypertension
Hypercalciuria
Hypocalcaemia
Decreased bone mineral density
Renal calcium stones
Treatable with thiazide diuretics
Variable age of onset from infancy to adulthood but highly effective treatment so leaning toward include.
Sources: Expert list
BabyScreen+ newborn screening v0.1952 ZBTB24 Lilian Downie gene: ZBTB24 was added
gene: ZBTB24 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB24 were set to PMID: 28128455, 21906047, 21596365, 23486536
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 MIM#614069
Review for gene: ZBTB24 was set to AMBER
Added comment: INfant onset
Agammaglobulinemia, facial anomalies, and mental retardation. Facial anomalies included broad, flat nasal bridge, hypertelorism, and epicanthal folds.
Treat immunoglobulin and bone marrow transplant however, this only treats the immune deficiency
Consider exclusion due to untreatable ID phenotype?
Sources: Expert list
BabyScreen+ newborn screening v0.1952 FOLR1 Zornitza Stark Marked gene: FOLR1 as ready
BabyScreen+ newborn screening v0.1951 FOLR1 Zornitza Stark gene: FOLR1 was added
gene: FOLR1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: FOLR1.
Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOLR1 were set to 19732866; 30420205; 27743887
Phenotypes for gene: FOLR1 were set to Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068
Review for gene: FOLR1 was set to GREEN
Added comment: Folate is a neurotransmitter precursor. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Recognition and diagnosis of this disorder is critical because folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function.

Treatment: folinic acid

Non-genetic confirmatory testing: cerebrospinal fluid 5-methyltetrahydrofolate level
Sources: Expert list
BabyScreen+ newborn screening v0.1950 FCHO1 Zornitza Stark Marked gene: FCHO1 as ready
BabyScreen+ newborn screening v0.1949 FCHO1 Zornitza Stark gene: FCHO1 was added
gene: FCHO1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: FCHO1.
Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FCHO1 were set to 32098969; 30822429
Phenotypes for gene: FCHO1 were set to Immunodeficiency 76, MIM# 619164
Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data.

Immunodeficiency-76 (IMD76) is an autosomal recessive primary immunologic disorder characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show T-cell lymphopenia and may show variable B-cell or immunoglobulin abnormalities. More variable features found in some patients include lymphoma and neurologic features.

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile, immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1948 FAM111A Zornitza Stark Marked gene: FAM111A as ready
BabyScreen+ newborn screening v0.1947 FAM111A Zornitza Stark gene: FAM111A was added
gene: FAM111A was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: FAM111A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FAM111A were set to Kenny-Caffey syndrome, type 2, MIM# 127000
Review for gene: FAM111A was set to GREEN
Added comment: Condition is characterised by impaired skeletal development with small and dense bones, short stature, ocular abnormalities, and primary hypoparathyroidism with hypocalcemia. At least 10 unrelated cases reported with de novo missense variants. Intellectual disability/developmental delay is a rare feature of the condition.

Treatment: magnesium, calcium and calcitriol or alfacalcidol

Non-genetic confirmatory testing: serum calcium, parathyroid hormone level, calcitonin level
Sources: Expert Review
BabyScreen+ newborn screening v0.1946 ERCC6L2 Zornitza Stark Marked gene: ERCC6L2 as ready
BabyScreen+ newborn screening v0.1945 ERCC6L2 Zornitza Stark gene: ERCC6L2 was added
gene: ERCC6L2 was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, haematological tags were added to gene: ERCC6L2.
Mode of inheritance for gene: ERCC6L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC6L2 were set to 24507776; 27185855
Phenotypes for gene: ERCC6L2 were set to Bone marrow failure syndrome 2, MIM# 615715
Review for gene: ERCC6L2 was set to AMBER
Added comment: Trilineage bone marrow failure, learning disabilities, and microcephaly. Three consanguineous families reported, but two with the same truncating variant, founder effect likely.

Treatment: bone marrow transplant.

Amber rating due to limited number of families reported.
Sources: Expert Review
BabyScreen+ newborn screening v0.1944 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
BabyScreen+ newborn screening v0.1943 DOCK2 Zornitza Stark gene: DOCK2 was added
gene: DOCK2 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DOCK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOCK2 were set to 26083206; 29204803; 33928462; 30826364; 30838481; 11518968
Phenotypes for gene: DOCK2 were set to Immunodeficiency 40 MIM# 616433
Review for gene: DOCK2 was set to GREEN
Added comment: 13 unrelated individuals; two mouse models; 10 biallelic mutations found (6 led to premature termination of the protein & 4 missense mutations affecting conserved residues) All patients presented with combined immunodeficiency in infancy (defective IFN-mediated immunity), early onset of invasive bacterial and viral infections, functional defects in T/B/NK cells and elevated IgM (normal IgG/IgA).

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert Review
BabyScreen+ newborn screening v0.1942 DNASE2 Zornitza Stark Marked gene: DNASE2 as ready
BabyScreen+ newborn screening v0.1941 DNASE2 Zornitza Stark gene: DNASE2 was added
gene: DNASE2 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNASE2 were set to 29259162; 31775019
Phenotypes for gene: DNASE2 were set to Autoinflammatory-pancytopenia syndrome, MIM# 619858
Review for gene: DNASE2 was set to GREEN
Added comment: Inflammatory disorder characterized by splenomegaly, glomerulonephritis, liver fibrosis, circulating anti-DNA autoantibodies, and progressive arthritis. Three families and functional data.

Treatment: baricitinib

Non-genetic confirmatory testing: Interferon signature
Sources: Expert Review
BabyScreen+ newborn screening v0.1940 DNAJC21 Zornitza Stark Marked gene: DNAJC21 as ready
BabyScreen+ newborn screening v0.1939 DNAJC21 Zornitza Stark gene: DNAJC21 was added
gene: DNAJC21 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DNAJC21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC21 were set to 29700810; 28062395; 27346687
Phenotypes for gene: DNAJC21 were set to Bone marrow failure syndrome 3, MIM# 617052
Review for gene: DNAJC21 was set to GREEN
Added comment: Onset of pancytopenia in early childhood; variable nonspecific somatic abnormalities, including poor growth, microcephaly, and skin anomalies.

Treatment: oral pancreatic enzymes, fat-soluble vitamins, blood and/or platelet transfusions, granulocyte-colony stimulation factor, bone marrow transplant

Confirmatory non-genetic testing: no; FBE as pancytopenia evolves.
Sources: Expert Review
BabyScreen+ newborn screening v0.1938 CYP2R1 Zornitza Stark Marked gene: CYP2R1 as ready
BabyScreen+ newborn screening v0.1937 CYP2R1 Zornitza Stark gene: CYP2R1 was added
gene: CYP2R1 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: CYP2R1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2R1 were set to 15128933; 28548312
Phenotypes for gene: CYP2R1 were set to Rickets due to defect in vitamin D 25-hydroxylation deficiency MIM#600081
Review for gene: CYP2R1 was set to GREEN
Added comment: At least 6 unrelated families reported.

Onset is generally in infancy.

Good response to vitamin D (calcifediol (25_OH_D3).

Confirmatory non-genetic testing: serum calcium, parathyroid hormone, 25-hydroxy vitamin D levels
Sources: Expert Review
BabyScreen+ newborn screening v0.1936 C17orf62 Zornitza Stark Marked gene: C17orf62 as ready
BabyScreen+ newborn screening v0.1935 C17orf62 Zornitza Stark gene: C17orf62 was added
gene: C17orf62 was added to Baby Screen+ newborn screening. Sources: Expert Review
new gene name, treatable, immunological tags were added to gene: C17orf62.
Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf62 were set to 30361506; 30312704; 28351984
Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Review for gene: C17orf62 was set to GREEN
Added comment: Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name)

Primary immunodeficiency characterized by onset of recurrent infections and severe colitis in the first decade of life. Patients often present with features of inflammatory bowel disease and may show granulomata on biopsy. Patients are particularly susceptible to catalase-positive organisms, including Burkholderia cepacia, Legionella, and Candida albicans. Some patients may develop autoinflammatory symptoms, including recurrent fever in the absence of infection, hemolytic anemia, and lymphopenia. Additional features may include short stature, viral infections, cutaneous abscesses, pulmonary infections, and lymphadenitis. Haematopoietic bone marrow transplant is curative.

Non-genetic confirmatory assay: dihydrorhodamine assay
Sources: Expert Review
BabyScreen+ newborn screening v0.1934 CYB561 Zornitza Stark Marked gene: CYB561 as ready
BabyScreen+ newborn screening v0.1933 CYB561 Zornitza Stark gene: CYB561 was added
gene: CYB561 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CYB561 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB561 were set to 29343526; 31822578
Phenotypes for gene: CYB561 were set to Orthostatic hypotension 2, MIM# 618182
Review for gene: CYB561 was set to GREEN
Added comment: Three families reported.

Severe orthostatic hypotension, recurrent hypoglycemia, and low norepinephrine levels. The disorder has onset in infancy or early childhood.

Treatment: L-threo-3,4-dihydroxyphenylserine (droxidopa)

Non-genetic confirmatory testing: plasma norepinephrine, epinephrine, dopamine
Sources: Expert list
BabyScreen+ newborn screening v0.1931 CR2 Zornitza Stark Marked gene: CR2 as ready
BabyScreen+ newborn screening v0.1931 CR2 Zornitza Stark Phenotypes for gene: CR2 were changed from Hypogammaglobulinaemia to Immunodeficiency, common variable, 7, MIM# 614699
BabyScreen+ newborn screening v0.1930 CR2 Zornitza Stark reviewed gene: CR2: Rating: RED; Mode of pathogenicity: None; Publications: 22035880, 26325596; Phenotypes: Immunodeficiency, common variable, 7, MIM# 614699; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1930 CORO1A Zornitza Stark Marked gene: CORO1A as ready
BabyScreen+ newborn screening v0.1929 CORO1A Zornitza Stark gene: CORO1A was added
gene: CORO1A was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CORO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CORO1A were set to Immunodeficiency 8 MIM# 615401
Review for gene: CORO1A was set to GREEN
Added comment: 3 unrelated families and 1 unrelated individual reported with bi-allelic (deletion, missense, insertion) variants, resulting in premature stop codons and truncated protein/ alter a highly conserved residue in binding domain; one mouse model

All patients displayed T−B+NK+ SCID or CID presenting in early-onset recurrent infections and additional features that included EBV-associated lymphoproliferative disease and low immunoglobulin levels.

Congenital onset.

Treatment: bone marrow transplant

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert list
BabyScreen+ newborn screening v0.1928 CDCA7 Zornitza Stark Marked gene: CDCA7 as ready
BabyScreen+ newborn screening v0.1927 CDCA7 Zornitza Stark gene: CDCA7 was added
gene: CDCA7 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CDCA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDCA7 were set to 26216346
Phenotypes for gene: CDCA7 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 3, MIM# 616910
Review for gene: CDCA7 was set to GREEN
Added comment: Congenital onset, severe disorder. At least 4 unrelated families reported.

Treatment: replacement immunoglobulins, bone marrow transplant

Non-genetic confirmatory testing: immunoglobulin levels, cytogenetic analysis for centromeric instability, DNA methylation studies
Sources: Expert Review
BabyScreen+ newborn screening v0.1926 CD81 Zornitza Stark Marked gene: CD81 as ready
BabyScreen+ newborn screening v0.1926 CD81 Zornitza Stark gene: CD81 was added
gene: CD81 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD81 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD81 were set to 20237408
Phenotypes for gene: CD81 were set to Immunodeficiency, common variable, 6, MIM# 613496
Review for gene: CD81 was set to RED
Added comment: CVID, which would be congenital, severe and treatable with replacement immunoglobulins.

However, only a single individual reported.
Sources: Expert Review
BabyScreen+ newborn screening v0.1925 CD70 Zornitza Stark Marked gene: CD70 as ready
BabyScreen+ newborn screening v0.1924 CD70 Zornitza Stark gene: CD70 was added
gene: CD70 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CD70 were set to Lymphoproliferative syndrome 3, MIM# 618261
Review for gene: CD70 was set to GREEN
Added comment: Severe lymphoproliferation following EBV infection.

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert Review
BabyScreen+ newborn screening v0.1923 CD55 Zornitza Stark Marked gene: CD55 as ready
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Marked gene: CD40 as ready
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Marked gene: CD40 as ready
BabyScreen+ newborn screening v0.1920 CD40 Zornitza Stark gene: CD40 was added
gene: CD40 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD40 were set to 29884852
Phenotypes for gene: CD40 were set to Immunodeficiency with hyper-IgM, type 3, MIM# 606843
Review for gene: CD40 was set to GREEN
Added comment: Severity can be variable but generally congenital onset, and predisposition to severe infections. Note CD40L already included.

Treatment: bone marrow transplantation.

Non-genetic confirmatory testing: immunoglobulin levels, flow cytometric analysis
Sources: Expert list
BabyScreen+ newborn screening v0.1919 CD3G Zornitza Stark Marked gene: CD3G as ready
BabyScreen+ newborn screening v0.1918 CD3G Zornitza Stark gene: CD3G was added
gene: CD3G was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD3G was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD3G were set to 31921117
Phenotypes for gene: CD3G were set to Immunodeficiency 17; CD3 gamma deficient MIM# 615607
Added comment: 10 affected individuals from 5 unrelated families; homozygous and compound heterozygous variants (splicing, missense and small deletion variants) identified resulting in premature stop codons and truncated protein; multiple mouse models.

All individuals displayed immune deficiency and autoimmunity of variable severity. Some individuals presented at birth with failure to thrive due to lethal SCID features. The most common immunologic profile includes partial T lymphocytopenia and low CD3, with normal B cells, NK cells, and immunoglobulins.

Congenital onset.

Treatment: replacement immunoglobulin

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1917 CD27 Zornitza Stark Marked gene: CD27 as ready
BabyScreen+ newborn screening v0.1916 CD27 Zornitza Stark gene: CD27 was added
gene: CD27 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD27 were set to 22197273; 22801960; 22365582; 25843314; 11062504
Phenotypes for gene: CD27 were set to CD27-deficiency MIM# 615122
Review for gene: CD27 was set to GREEN
Added comment: 17 affected individuals from 9 unrelated families; homozygous (missense) and compound heterozygous (missense/ nonsense) variants identified in CD27; one mouse model. Affected individuals present with varied phenotypes (even within the same families); most commonly with lymphadenopathy, fever, hepatosplenomegaly, EBV-related infections, and immunodeficiency associated with hypogammaglobulinaemia. However, some CD27-deficient individuals are asymptomatic or display borderline-low hypogammaglobulinaemia.

Treatment: replacement immunoglobulin treatment, rituximab, Bone marrow transplant.

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1915 CD247 Zornitza Stark Marked gene: CD247 as ready
BabyScreen+ newborn screening v0.1914 CD247 Zornitza Stark gene: CD247 was added
gene: CD247 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD247 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD247 were set to 16672702; 17170122
Phenotypes for gene: CD247 were set to Immunodeficiency 25, MIM# 610163
Review for gene: CD247 was set to GREEN
Added comment: Two reports in the literature, note additional two reports in ClinVar; functional data.

Congenital onset. Absent T cells, resulting in severe immunodeficiency.

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T, B and NK cell counts
Sources: Expert Review
BabyScreen+ newborn screening v0.1913 CD19 Zornitza Stark Marked gene: CD19 as ready
BabyScreen+ newborn screening v0.1912 CD19 Zornitza Stark gene: CD19 was added
gene: CD19 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CD19 were set to Immunodeficiency, common variable, 3, MIM# 613493
Review for gene: CD19 was set to GREEN
Added comment: More than 5 unrelated families reported. Clinical features include increased susceptibility to infection, hypogammaglobulinaemia, and normal numbers of mature B cells in blood, indicating a B-cell antibody-deficient immunodeficiency disorder.

Onset is congenital.

Treatment: IVIG

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1911 CAV1 Zornitza Stark Marked gene: CAV1 as ready
BabyScreen+ newborn screening v0.1908 PRDX1 Zornitza Stark Marked gene: PRDX1 as ready
BabyScreen+ newborn screening v0.1907 PNP Zornitza Stark Marked gene: PNP as ready
BabyScreen+ newborn screening v0.1906 MTHFR Zornitza Stark Marked gene: MTHFR as ready
BabyScreen+ newborn screening v0.1903 MCCC2 Zornitza Stark Marked gene: MCCC2 as ready
BabyScreen+ newborn screening v0.1903 MCCC2 Zornitza Stark Phenotypes for gene: MCCC2 were changed from 3-Methylcrotonyl-CoA carboxylase 2 deficiency; 3-Methylcrotonyl-CoA carboxylase 2 deficiency, MIM# 210210 to 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210
BabyScreen+ newborn screening v0.1901 MCCC2 Zornitza Stark reviewed gene: MCCC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1901 MCCC1 Zornitza Stark Marked gene: MCCC1 as ready
BabyScreen+ newborn screening v0.1901 MCCC1 Zornitza Stark Phenotypes for gene: MCCC1 were changed from 3-Methylcrotonyl-CoA carboxylase 1 deficiency; 3-Methylcrotonyl-CoA carboxylase 1 deficiency, MIM# 210200 to 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200
BabyScreen+ newborn screening v0.1898 MCCC1 Zornitza Stark reviewed gene: MCCC1: Rating: RED; Mode of pathogenicity: None; Publications: 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1898 MAT1A Zornitza Stark Marked gene: MAT1A as ready
BabyScreen+ newborn screening v0.1896 LIAS Zornitza Stark Marked gene: LIAS as ready
BabyScreen+ newborn screening v0.1891 HPD Zornitza Stark Marked gene: HPD as ready
BabyScreen+ newborn screening v0.1890 HMGCS2 Zornitza Stark Marked gene: HMGCS2 as ready
BabyScreen+ newborn screening v0.1889 HIBCH Zornitza Stark Marked gene: HIBCH as ready
BabyScreen+ newborn screening v0.1886 GLIS3 Zornitza Stark Marked gene: GLIS3 as ready
BabyScreen+ newborn screening v0.1883 PRDX1 Lilian Downie gene: PRDX1 was added
gene: PRDX1 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to PMID: 20301503, PMID: 29396438, PMID: 34215320, PMID: 33982424
Phenotypes for gene: PRDX1 were set to Methylmalonic aciduria and homocystinuria, cblC type, digenic MIM#277400
Review for gene: PRDX1 was set to GREEN
Added comment: Digenic inheritance with mutation in other allele of MMACHC
On GUARDIAN and Rx genes list

Recently, three individuals who are double heterozygous for pathogenic variants in MMACHC and PRDX1 have been identified. PRDX1 is a neighboring gene on chromosome 1 transcribed from the reverse strand. Variants identified in PRDX1 located at the intron 5 splice acceptor site caused skipping of exon 6, transcription of antisense MMACHC, and hypermethylation of the MMACHC promoter/exon 1, resulting in no gene expression from that allele [Guéant et al 2018].

Treatable with cobalamin, carnitine & diet. NB MMACHC is green on our list, on newborn screening.
Sources: Expert list
BabyScreen+ newborn screening v0.1883 PNP Lilian Downie gene: PNP was added
gene: PNP was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNP were set to PMID: 35968787, PMID: 35063692, PMID: 30885031, PMID: 1931007, PMID: 28674683
Phenotypes for gene: PNP were set to Immunodeficiency due to purine nucleoside phosphorylase deficiency MIM#613179
Review for gene: PNP was set to GREEN
Added comment: Decreased T cell function - SCID immunodeficiency
variable neurological phenotype
childhood onset
Treat bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.1883 MCCC2 Lilian Downie reviewed gene: MCCC2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22642865; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1883 GATM Zornitza Stark Marked gene: GATM as ready
BabyScreen+ newborn screening v0.1882 FOXE1 Zornitza Stark Marked gene: FOXE1 as ready
BabyScreen+ newborn screening v0.1882 FOXE1 Zornitza Stark Phenotypes for gene: FOXE1 were changed from Bamforth-Lazarus syndrome to Bamforth-Lazarus syndrome MIM# 241850
BabyScreen+ newborn screening v0.1879 ALDH4A1 Zornitza Stark Marked gene: ALDH4A1 as ready
BabyScreen+ newborn screening v0.1876 ACADSB Zornitza Stark Marked gene: ACADSB as ready
BabyScreen+ newborn screening v0.1875 ACADS Zornitza Stark Marked gene: ACADS as ready
BabyScreen+ newborn screening v0.1875 ABCD4 Zornitza Stark Marked gene: ABCD4 as ready
BabyScreen+ newborn screening v0.1872 MCCC1 Lilian Downie reviewed gene: MCCC1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 22642865; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 LIAS Lilian Downie gene: LIAS was added
gene: LIAS was added to gNBS. Sources: Expert list
Mode of inheritance for gene: LIAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIAS were set to PMID: 24334290, 24777537,
Phenotypes for gene: LIAS were set to Hyperglycinemia, lactic acidosis, and seizures MIM#614462
Review for gene: LIAS was set to RED
Added comment: pyruvate dehydrogenase lipoic acid synthetase deficiency (PDHLD)
increased serum glycine and lactate in the first days of life, hypotonia, seizures, early death
No treatment
Sources: Expert list
BabyScreen+ newborn screening v0.1872 HMGCS2 Lilian Downie gene: HMGCS2 was added
gene: HMGCS2 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: HMGCS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCS2 were set to PMID: 32259399, 32470406
Phenotypes for gene: HMGCS2 were set to HMG-CoA synthase-2 deficiency MIM#605911
Penetrance for gene: HMGCS2 were set to Incomplete
Review for gene: HMGCS2 was set to AMBER
Added comment: Metabolic disorder; patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting. Recover completely between illnesses, do develop fatty liver.
?incomplete penetrance or variable age of onset
On GUARDIAN and Rx Genes
Rx IV glucose during acute episodes, avoid prolonged fasting
Metabolic parameters are normal in between episodes, so no ability to do a confirmatory biochemical test.
Pros: readily treatable if child has an episode Cons: unncessary worry as child may never have episode
Super rare ?30 cases
Discuss with JC?
Sources: Expert list
BabyScreen+ newborn screening v0.1872 GATM Lilian Downie gene: GATM was added
gene: GATM was added to gNBS. Sources: Expert list
Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATM were set to PMID: 20301745, 34972654
Phenotypes for gene: GATM were set to Cerebral creatine deficiency syndrome 3 MIM#612718
Review for gene: GATM was set to GREEN
Added comment: GUARDIAN gene list (not on babyseq or rxgenes)
ID and myopathy, early onset
Rx creatine
Seems like a good fit? I'm not clear from the literature how effective the treatment is. check with JC
Sources: Expert list
BabyScreen+ newborn screening v0.1872 FOXE1 Lilian Downie reviewed gene: FOXE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33272083, 2918525, 20453517, 35963604; Phenotypes: Bamforth-Lazarus syndrome MIM# 241850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
BabyScreen+ newborn screening v0.1872 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from Cardiomyopathy; Metabolic Crises; Arrhythmia; Neurodevelopmental to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
BabyScreen+ newborn screening v0.1868 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
BabyScreen+ newborn screening v0.1868 NKX2-5 Zornitza Stark Phenotypes for gene: NKX2-5 were changed from Congenital heart disease to Atrial septal defect 7, with or without AV conduction defects, MIM# 108900
BabyScreen+ newborn screening v0.1867 NKX2-5 Zornitza Stark Tag cardiac tag was added to gene: NKX2-5.
BabyScreen+ newborn screening v0.1865 HADHA Ari Horton reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31575911; Phenotypes: Cardiomyopathy, Metabolic Disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1865 TANGO2 Ari Horton changed review comment from: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review; to: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

PMID: 35568137

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4–9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all (median 547 ms; IQR 504–600 ms) and a type I Brugada pattern in 8 (26%). Arrhythmias included VT in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest. There were 10 deaths (37%), 6 related to arrhythmias. In 5 patients, recalcitrant VT occurred despite use of antiarrhythmic drugs. In 6 patients, arrhythmias were controlled after extracorporeal membrane oxygenation (ECMO) support; 5 of these patients survived. Among 10 patients who survived VT without ECMO, successful treatment included intravenous magnesium, isoproterenol, and atrial pacing in multiple cases and verapamil in 1 patient. Initiation of feeds seemed to decrease VT events.

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review
BabyScreen+ newborn screening v0.1865 TANGO2 Ari Horton gene: TANGO2 was added
gene: TANGO2 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TANGO2 were set to Cardiomyopathy; Metabolic Crises; Arrhythmia; Neurodevelopmental
Penetrance for gene: TANGO2 were set to Complete
Review for gene: TANGO2 was set to GREEN
Added comment: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review
BabyScreen+ newborn screening v0.1865 LAMP2 Ari Horton reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Childhood onset cardiomyopathy (Severe), Neuordevelopmental phenotype; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1865 NKX2-5 Ari Horton reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neonatal onset cardiomyopathy, Congenital Heart Disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
BabyScreen+ newborn screening v0.1865 GATA4 Ari Horton reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, Congenital Heart Disease, Arrhythmia, Extra-cardiac Manifestations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
BabyScreen+ newborn screening v0.1862 MCFD2 Zornitza Stark Marked gene: MCFD2 as ready
BabyScreen+ newborn screening v0.1862 HBB Zornitza Stark changed review comment from: Well established gene-disease associations.

Congenital onset.

Both sickle cell anaemia and beta thalassaemia are treatable disorders.

Beta thal: gene therapy (betibeglogene autotemcel - clinical trial), red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), Luspatercept

Sickle cell: glutamine, voxelotor, crizanlizumab, hydroxyurea, ,red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), gene therapy (BCH-BB694 BCL11A shmiR lentiviral vector - clinical trial and autologous CRISPR-Cas9-edited CD34+ hematopoietic stem and progenitor cells) - clinical trial)

Some of the beta-that variants are structural -- ability to detect reliably? For review.; to: Well established gene-disease associations.

Congenital onset.

Both sickle cell anaemia and beta thalassaemia are treatable disorders.

Beta thal: gene therapy (betibeglogene autotemcel - clinical trial), red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), Luspatercept

Sickle cell: glutamine, voxelotor, crizanlizumab, hydroxyurea, ,red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), gene therapy (BCH-BB694 BCL11A shmiR lentiviral vector - clinical trial and autologous CRISPR-Cas9-edited CD34+ hematopoietic stem and progenitor cells) - clinical trial)

Some of the beta-that variants are structural -- ability to detect reliably? For review.

We are only able to reliably screen for the HbS association.
BabyScreen+ newborn screening v0.1860 HBA1 Zornitza Stark changed review comment from: Well established gene-disease association.

Congenital onset.

Treatable: transfusions, bone marrow transplant.

However, there is widespread screening in pregnancy. Also note mutational spectrum includes SVs/CNVs: can we reliably diagnose? For review.; to: Well established gene-disease association.

Congenital onset.

Treatable: transfusions, bone marrow transplant.

However, there is widespread screening in pregnancy. Also note mutational spectrum includes SVs/CNVs: can we reliably diagnose?

Exclude for now due to technical concerns.
BabyScreen+ newborn screening v0.1859 F8 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity.

Treatment: recombinant factor VIII. Gene therapy trial.

Non-genetic confirmatory testing: factor VIII levels.

Note: excluded from other screening tests due to concerns regarding ability to detect the intron 22 inversion (Inv22) mutation of F8 which causes about 45% of severe HA cases. For review.; to: Well established gene-disease association.

Variable severity.

Treatment: recombinant factor VIII. Gene therapy trial.

Non-genetic confirmatory testing: factor VIII levels.

Note: excluded from other screening tests due to concerns regarding ability to detect the intron 22 inversion (Inv22) mutation of F8 which causes about 45% of severe HA cases. Intron 1 inversion also common.

Excluded for now until we can confirm we can detect inversion.
BabyScreen+ newborn screening v0.1858 TBX1 Zornitza Stark reviewed gene: TBX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: DiGeorge syndrome MIM# 188400, Velocardiofacial syndrome MIM# 192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1852 JUP Zornitza Stark edited their review of gene: JUP: Added comment: Screen for bi-allelic disease as can be earlier onset, more severe.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1850 DSP Zornitza Stark edited their review of gene: DSP: Added comment: Screen for bi-allelic disease as can be more severe, earlier onset.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1850 CALM3 Zornitza Stark Phenotypes for gene: CALM3 were changed from Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782 to Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782; Long QT syndrome 16, MIM#618782
BabyScreen+ newborn screening v0.1849 CALM3 Zornitza Stark edited their review of gene: CALM3: Added comment: Variants in this gene also cause Long QT syndrome, and other Long QT syndrome genes have been included in the panel.; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782, Long QT syndrome 16, MIM#618782
BabyScreen+ newborn screening v0.1849 LAMP2 Zornitza Stark Tag cardiac tag was added to gene: LAMP2.
BabyScreen+ newborn screening v0.1849 TRPM4 Zornitza Stark Tag cardiac tag was added to gene: TRPM4.
BabyScreen+ newborn screening v0.1849 TMEM43 Zornitza Stark changed review comment from: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.; to: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.

Note founder variant in Newfoundland.
BabyScreen+ newborn screening v0.1845 CASQ2 Zornitza Stark changed review comment from: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

For review.; to: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.
BabyScreen+ newborn screening v0.1844 CAD Zornitza Stark Marked gene: CAD as ready
BabyScreen+ newborn screening v0.1843 CAD Zornitza Stark gene: CAD was added
gene: CAD was added to gNBS. Sources: Expert list
treatable, metabolic tags were added to gene: CAD.
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 28007989
Phenotypes for gene: CAD were set to Developmental and epileptic encephalopathy 50, MIM# 616457
Review for gene: CAD was set to GREEN
Added comment: Developmental and epileptic encephalopathy-50 (DEE50) is an autosomal recessive progressive neurodegenerative neurometabolic disorder characterized by delayed psychomotor development, early-onset refractory seizures, severe developmental regression, and normocytic anemia. Onset is within the first months or years of life.

Affected children can have a favourable response to treatment with uridine, PMID 28007989
Sources: Expert list
BabyScreen+ newborn screening v0.1842 CA12 Zornitza Stark Marked gene: CA12 as ready
BabyScreen+ newborn screening v0.1840 AICDA Zornitza Stark Marked gene: AICDA as ready
BabyScreen+ newborn screening v0.1839 AICDA Zornitza Stark gene: AICDA was added
gene: AICDA was added to gNBS. Sources: Expert Review
treatable, immunological tags were added to gene: AICDA.
Mode of inheritance for gene: AICDA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AICDA were set to Immunodeficiency with hyper-IgM, type 2, MIM# 605258
Review for gene: AICDA was set to GREEN
Added comment: Hyper-IgM syndrome type 2 (HIGM2) is a rare immunodeficiency characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. Well established gene-disease association.

Severe, congenital disorder.

Treatment: immunoglobulin replacement therapy.

Confirmatory testing: antibody levels.
Sources: Expert Review
BabyScreen+ newborn screening v0.1838 AGPAT2 Zornitza Stark Marked gene: AGPAT2 as ready
BabyScreen+ newborn screening v0.1837 AGPAT2 Zornitza Stark gene: AGPAT2 was added
gene: AGPAT2 was added to gNBS. Sources: Expert list
for review, treatable, endocrine tags were added to gene: AGPAT2.
Mode of inheritance for gene: AGPAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGPAT2 were set to 29704234
Phenotypes for gene: AGPAT2 were set to Lipodystrophy, congenital generalized, type 1, MIM# 608594
Review for gene: AGPAT2 was set to AMBER
Added comment: Established gene-disease association.

Congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, is a rare autosomal recessive disease characterized by a near absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biologic features include acanthosis nigricans, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia.

Leptin replacement therapy (metreleptin) has been found to improve metabolic parameters in many patients with lipodystrophy. Metreleptin is approved in the United States as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy and has been submitted for approval elsewhere.

For review regarding availability and use of treatment locally.
Sources: Expert list
BabyScreen+ newborn screening v0.1834 WT1 Zornitza Stark changed review comment from: Rated as 'moderate actionability' in paediatric patients by ClinGen.

Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%.

The goal of surveillance in individuals with a genetic predisposition to WT is to

detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome.

No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms.

Penetrance is unclear. For review.; to: Rated as 'moderate actionability' in paediatric patients by ClinGen.

Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%.

The goal of surveillance in individuals with a genetic predisposition to WT is to

detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome.

No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms.
BabyScreen+ newborn screening v0.1834 GLA Zornitza Stark changed review comment from: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started.; to: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started. Note ERT is licensed in Australia from age 7 years.

However, carbamazepine relieves neuropathic pain, which has onset in early childhood. Overall, include.
BabyScreen+ newborn screening v0.1834 SMAD2 Zornitza Stark Marked gene: SMAD2 as ready
BabyScreen+ newborn screening v0.1833 SMAD2 Zornitza Stark Tag cardiac tag was added to gene: SMAD2.
Tag treatable tag was added to gene: SMAD2.
BabyScreen+ newborn screening v0.1833 SMAD2 Zornitza Stark gene: SMAD2 was added
gene: SMAD2 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: SMAD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome 6, MIM# 619656
Review for gene: SMAD2 was set to GREEN
Added comment: 9 individuals from 5 unrelated families reported with LDS phenotype. Gene-disease association rated 'moderate' by ClinGen but this gene is included in our diagnostic testing.

LDS included in gNBS panel as in general medical actionability for the LDS group of disorders is considered established.

Can manifest in early childhood.

Treatment: different interventions, including beta-blockers, surgical and monitoring

Non-genetic confirmatory test: characteristic clinical findings
Sources: Expert Review
BabyScreen+ newborn screening v0.1825 PMM2 Zornitza Stark changed review comment from: Well established gene-disease association.

Two clinical presentations - solely neurologic form and a neurologic-multivisceral form
Mortality approximately 20% in first 2 years

Treatment: epalrestat

PMID 31636082: Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations.

For review: uncertain if in use for CDG; to: Well established gene-disease association.

Two clinical presentations - solely neurologic form and a neurologic-multivisceral form
Mortality approximately 20% in first 2 years

Treatment: epalrestat

PMID 31636082: Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations.

Treatment not well established in patients.
BabyScreen+ newborn screening v0.1823 HPRT1 Zornitza Stark changed review comment from: Uncertain if these are essentially symptomatic treatments.; to: Symptomatic treatments.
BabyScreen+ newborn screening v0.1822 FBN1 Zornitza Stark Tag for review was removed from gene: FBN1.
Tag cardiac tag was added to gene: FBN1.
Tag treatable tag was added to gene: FBN1.
BabyScreen+ newborn screening v0.1821 RET Zornitza Stark changed review comment from: Established gene-disease associations.

Assessed as 'strong actionability' in paediatric patients by ClinGen.

Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A.

PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age.

For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age.

Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients.

Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants.

For review: actionable in first 5 years of life?; to: Established gene-disease associations.

Assessed as 'strong actionability' in paediatric patients by ClinGen.

Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A.

PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age.

For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age.

Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients.

Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants.

For review: some actionability in first 5 years, variants can be stratified in terms of risk.
BabyScreen+ newborn screening v0.1821 PRKAR1A Zornitza Stark Tag for review was removed from gene: PRKAR1A.
BabyScreen+ newborn screening v0.1820 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
BabyScreen+ newborn screening v0.1818 DHFR Zornitza Stark Marked gene: DHFR as ready
BabyScreen+ newborn screening v0.1816 DNAJC12 Zornitza Stark Marked gene: DNAJC12 as ready
BabyScreen+ newborn screening v0.1815 DNAJC12 Zornitza Stark gene: DNAJC12 was added
gene: DNAJC12 was added to gNBS. Sources: Expert Review
treatable, metabolic tags were added to gene: DNAJC12.
Mode of inheritance for gene: DNAJC12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAJC12 were set to Hyperphenylalaninemia, mild, non-BH4-deficient, MIM#617384
Review for gene: DNAJC12 was set to GREEN
Added comment: Established gene-disease association.

Manifests as mild hyperphenylalaninaemia that would be detected on NBS – untreated results in axial hypotonia, dystonia, nystagmus, global developmental delay,
and intellectual disability.

From Treatable-ID, level 4 evidence that BH4, L-dopa + carbidopa +/-, 5-
hydroxytryptophan improves psychomotor/cognitive development/IQ; prevents, halts, or slows clinical deterioration and improves neurological manifestations.
Sources: Expert Review
BabyScreen+ newborn screening v0.1814 GALM Zornitza Stark Marked gene: GALM as ready
BabyScreen+ newborn screening v0.1812 GCH1 Zornitza Stark Marked gene: GCH1 as ready
BabyScreen+ newborn screening v0.1807 PMS2 Zornitza Stark Marked gene: PMS2 as ready
BabyScreen+ newborn screening v0.1804 MSH6 Zornitza Stark Marked gene: MSH6 as ready
BabyScreen+ newborn screening v0.1801 MLH1 Zornitza Stark changed review comment from: Note mono-allelic variants are associated with adult-onset cancer risk.

MMRCS rated as 'strong actionability' in paediatric patients by ClinGen.

The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years.

The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested:

•Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended.
•Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age.
•Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years.
•Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician.
•For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years.
•Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years.
•To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI.

Estimated penetrance in MMRCS:

•50% develop small-bowel adenomas
•>90% develop colorectal adenomas
•59 to 70% develop colorectal cancer
•58 to 70% develop high-grade brain tumours
•20-40% develop lymphoma
•10-40% develop leukemia
•10 to 18% develop small-bowel cancer
•<10% develop endometrial cancer
•<10% develop urinary tract cancer

•<10% develop cancer of other sites; to: Note mono-allelic variants are associated with adult-onset cancer risk.

MMRCS rated as 'strong actionability' in paediatric patients by ClinGen.

The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years.

The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested:

•Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended.
•Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age.
•Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years.
•Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician.
•For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years.
•Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years.
•To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI.

Estimated penetrance in MMRCS:

•50% develop small-bowel adenomas
•>90% develop colorectal adenomas
•59 to 70% develop colorectal cancer
•58 to 70% develop high-grade brain tumours
•20-40% develop lymphoma
•10-40% develop leukemia
•10 to 18% develop small-bowel cancer
•<10% develop endometrial cancer
•<10% develop urinary tract cancer
•<10% develop cancer of other sites
BabyScreen+ newborn screening v0.1801 MLH1 Zornitza Stark Marked gene: MLH1 as ready
BabyScreen+ newborn screening v0.1799 TMPRSS3 Seb Lunke Marked gene: TMPRSS3 as ready
BabyScreen+ newborn screening v0.1797 MSH2 Zornitza Stark Marked gene: MSH2 as ready
BabyScreen+ newborn screening v0.1793 LYST Seb Lunke Marked gene: LYST as ready
BabyScreen+ newborn screening v0.1793 COL9A2 Seb Lunke Marked gene: COL9A2 as ready
BabyScreen+ newborn screening v0.1793 TPRN Zornitza Stark Marked gene: TPRN as ready
BabyScreen+ newborn screening v0.1790 S1PR2 Zornitza Stark Marked gene: S1PR2 as ready
BabyScreen+ newborn screening v0.1788 PTPRQ Zornitza Stark Marked gene: PTPRQ as ready
BabyScreen+ newborn screening v0.1785 OTOG Zornitza Stark Marked gene: OTOG as ready
BabyScreen+ newborn screening v0.1782 PRKG1 Zornitza Stark Marked gene: PRKG1 as ready
BabyScreen+ newborn screening v0.1781 PRKG1 Zornitza Stark gene: PRKG1 was added
gene: PRKG1 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: PRKG1.
Mode of inheritance for gene: PRKG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKG1 were set to Aortic aneurysm, familial thoracic 8, MIM#615436
Penetrance for gene: PRKG1 were set to Incomplete
Review for gene: PRKG1 was set to AMBER
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).
Sources: ClinGen
BabyScreen+ newborn screening v0.1780 MYH11 Zornitza Stark Marked gene: MYH11 as ready
BabyScreen+ newborn screening v0.1779 MYH11 Zornitza Stark Tag for review tag was added to gene: MYH11.
Tag cardiac tag was added to gene: MYH11.
Tag treatable tag was added to gene: MYH11.
BabyScreen+ newborn screening v0.1779 LOX Zornitza Stark Marked gene: LOX as ready
BabyScreen+ newborn screening v0.1778 LOX Zornitza Stark gene: LOX was added
gene: LOX was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: LOX.
Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10, MIM#617168
Penetrance for gene: LOX were set to Incomplete
Review for gene: LOX was set to AMBER
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.
Sources: ClinGen
BabyScreen+ newborn screening v0.1777 ACTA2 Zornitza Stark Marked gene: ACTA2 as ready
BabyScreen+ newborn screening v0.1776 ACTA2 Zornitza Stark Tag for review tag was added to gene: ACTA2.
Tag cardiac tag was added to gene: ACTA2.
Tag treatable tag was added to gene: ACTA2.
BabyScreen+ newborn screening v0.1775 MCEE Zornitza Stark Marked gene: MCEE as ready
BabyScreen+ newborn screening v0.1773 RUNX1 Zornitza Stark Marked gene: RUNX1 as ready
BabyScreen+ newborn screening v0.1772 RUNX1 Zornitza Stark gene: RUNX1 was added
gene: RUNX1 was added to gNBS. Sources: ClinGen
for review, treatable, haematological tags were added to gene: RUNX1.
Mode of inheritance for gene: RUNX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RUNX1 were set to Platelet disorder, familial, with associated myeloid malignancy, MIM# 601399
Review for gene: RUNX1 was set to AMBER
Added comment: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

HTHCPS is characterized by mild to moderate thrombocytopenia with normal platelet size, abnormal platelet functioning (defective release of delta granules and/or aggregation defects), and an increased risk of developing a haematologic malignancy.

Age of onset of bleeding can be highly variable, with some individuals presenting in early infancy and others not recognizing their symptoms until much later in life. Severe thrombocytopenia or profound platelet dysfunction can result in recognition during the perinatal or infancy period. Hematologic malignancies can occur in childhood or adulthood; the range of age of onset is wide with a median age of 33 years.

Use of clotting promotors (e.g., desmopressin, epsilon aminocaproic acid, tranexamic acid) can be used for surgeries, injuries, or dental treatments. Platelet transfusions may be used for severe bleeding or procedures with a high bleeding risk.

Though there is no specific treatment for HTHCPS, there are recommendations regarding the indications and timing of hematopoietic stem cell transplantation (HSCT) that vary. HSCT in pre-malignancy patients, particularly in the absence of any clonal progression, is debatable due to transplantation-associated risks and incomplete penetrance. Some suggested indications for HSCT include severe or symptomatic cytopenias, severe marrow dysplasia (particularly in the context of falling blood counts), complex or high-risk (e.g., monosomy 7) cytogenetic abnormalities (particularly if the clones are large or increasing in size) and increasing blasts >5%.

Consider use of a medical alert bracelet for thrombocytopenia, platelet dysfunction, or hematologic malignancy as indicated.
Sources: ClinGen
BabyScreen+ newborn screening v0.1771 DICER1 Zornitza Stark Marked gene: DICER1 as ready
BabyScreen+ newborn screening v0.1770 DICER1 Zornitza Stark gene: DICER1 was added
gene: DICER1 was added to gNBS. Sources: ClinGen
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DICER1 were set to DICER1 syndrome, MONDO:0017288
Penetrance for gene: DICER1 were set to Incomplete
Review for gene: DICER1 was set to AMBER
Added comment: Rated as 'moderate actionability' in paediatric patients by ClinGen.

A multiple registry study examining neoplasm incidence in a cohort containing 102 non-probands with DICER1 pathogenic variants (3,344 person-years of observation in non-probands) found that by age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of non-probands had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of non-probands had developed a neoplasm (females, 26.5%; males, 10.2%).

Most individuals with pathogenic variants in DICER1 are healthy or have only minor DICER1-associaited conditions. The most severe manifestations tend to present in early childhood with adulthood characterized by good health. The majority of tumors in individuals with DICER1 pathogenic variants occur in individuals younger than 40. Many of these tumors typically only occur in childhood, including: PPB (before age 7), CN (before age 4), CBME typically occurs in young children, pituitary blastoma (before age 2), and childhood pineoblastoma (only one has been reported associated with a DICER1 mutation).

Surveillance recommendations:
In order to detect pulmonary cysts or PPB (one of the most important causes of DICER1-associated morbidity and mortality), chest x-rays are recommended every 6 months from birth to through age 7 years and then annually from 8-12 years. A chest computed tomography (CT) (with efforts to minimize radiation) should be obtained by 9 months of age, preferably between 3 and 6 months of age and repeated at approximately 2.5 years of age.

Abdominal ultrasound is recommended for the detection in infancy or at the time of the first chest CT then every 6-12 months until at least 8 years of age. Annual ultrasound may be considered until 12 years of age.

Beginning at ages 8-10 females should receive pelvic ultrasound performed in conjunction with abdominal ultrasound (every 6-12 months) until at least age 40 or as needed for signs and symptoms.

Individuals should undergo thyroid ultrasound with assessment for regional adenopathy every 2 to 3 years starting at age 8 or as needed for signs and symptoms.

An annual routine dilated ophthalmologic exam with visual acuity screening is recommended from age 3 to at least age 10 for detection of CBME.
Sources: ClinGen
BabyScreen+ newborn screening v0.1769 BRCA1 Zornitza Stark Marked gene: BRCA1 as ready
BabyScreen+ newborn screening v0.1769 BRCA1 Zornitza Stark Phenotypes for gene: BRCA1 were changed from Breast-ovarian cancer, familial, 1 to Fanconi anemia, complementation group S, MIM# 617883
BabyScreen+ newborn screening v0.1766 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
BabyScreen+ newborn screening v0.1766 BRCA2 Zornitza Stark Phenotypes for gene: BRCA2 were changed from Fanconi anaemia, complementation group D, MIM#1 605724; Fanconi anemia, complementation group D1; Breast-ovarian cancer, familial, 2 to Fanconi anaemia, complementation group D1, MIM# 605724
BabyScreen+ newborn screening v0.1763 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
BabyScreen+ newborn screening v0.1762 KCNQ1 Zornitza Stark Tag for review tag was added to gene: KCNQ1.
Tag cardiac tag was added to gene: KCNQ1.
Tag treatable tag was added to gene: KCNQ1.
BabyScreen+ newborn screening v0.1762 KCNH2 Zornitza Stark Marked gene: KCNH2 as ready
BabyScreen+ newborn screening v0.1761 KCNH2 Zornitza Stark Tag for review tag was added to gene: KCNH2.
Tag cardiac tag was added to gene: KCNH2.
Tag treatable tag was added to gene: KCNH2.
BabyScreen+ newborn screening v0.1761 TMEM43 Zornitza Stark Tag for review tag was added to gene: TMEM43.
Tag cardiac tag was added to gene: TMEM43.
Tag treatable tag was added to gene: TMEM43.
BabyScreen+ newborn screening v0.1761 TMEM43 Zornitza Stark reviewed gene: TMEM43: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 5 MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1761 PKP2 Zornitza Stark Marked gene: PKP2 as ready
BabyScreen+ newborn screening v0.1761 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9 to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040
BabyScreen+ newborn screening v0.1760 PKP2 Zornitza Stark Tag for review tag was added to gene: PKP2.
Tag cardiac tag was added to gene: PKP2.
Tag treatable tag was added to gene: PKP2.
BabyScreen+ newborn screening v0.1760 PKP2 Zornitza Stark reviewed gene: PKP2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 9, MIM# 609040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1760 DSP Zornitza Stark Marked gene: DSP as ready
BabyScreen+ newborn screening v0.1760 DSP Zornitza Stark Phenotypes for gene: DSP were changed from Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676; Epidermolysis bullosa, lethal acantholytic; Arrhythmogenic right ventricular dysplasia/cardiomyopathy; Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis , MIM#615821 to Arrhythmogenic right ventricular dysplasia 8, MIM# 607450
BabyScreen+ newborn screening v0.1758 DSP Zornitza Stark Tag for review tag was added to gene: DSP.
Tag cardiac tag was added to gene: DSP.
Tag treatable tag was added to gene: DSP.
BabyScreen+ newborn screening v0.1758 DSP Zornitza Stark reviewed gene: DSP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 8, MIM# 607450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1758 DSG2 Zornitza Stark Marked gene: DSG2 as ready
BabyScreen+ newborn screening v0.1758 DSG2 Zornitza Stark Phenotypes for gene: DSG2 were changed from Arrhythmogenic right ventricular cardiomyopathy to Arrhythmogenic right ventricular dysplasia 10, MIM# 610193
BabyScreen+ newborn screening v0.1757 DSG2 Zornitza Stark Tag for review tag was added to gene: DSG2.
Tag cardiac tag was added to gene: DSG2.
Tag treatable tag was added to gene: DSG2.
BabyScreen+ newborn screening v0.1757 DSG2 Zornitza Stark reviewed gene: DSG2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 10, MIM# 610193; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1757 JUP Zornitza Stark Marked gene: JUP as ready
BabyScreen+ newborn screening v0.1757 JUP Zornitza Stark Phenotypes for gene: JUP were changed from Arrhythmogenic right ventricular dysplasia 12; Naxos disease to Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214
BabyScreen+ newborn screening v0.1756 JUP Zornitza Stark Tag for review tag was added to gene: JUP.
Tag cardiac tag was added to gene: JUP.
Tag treatable tag was added to gene: JUP.
BabyScreen+ newborn screening v0.1756 JUP Zornitza Stark reviewed gene: JUP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 12 MIM# 611528, Naxos disease MIM# 601214; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1756 DSC2 Zornitza Stark Marked gene: DSC2 as ready
BabyScreen+ newborn screening v0.1756 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from Arrhythmogenic right ventricular cardiomyopathy to Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
BabyScreen+ newborn screening v0.1754 DSC2 Zornitza Stark Tag for review tag was added to gene: DSC2.
Tag cardiac tag was added to gene: DSC2.
Tag treatable tag was added to gene: DSC2.
BabyScreen+ newborn screening v0.1754 DSC2 Zornitza Stark reviewed gene: DSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 11, MIM# 610476, Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1754 OAT Zornitza Stark Marked gene: OAT as ready
BabyScreen+ newborn screening v0.1753 OAT Zornitza Stark gene: OAT was added
gene: OAT was added to gNBS. Sources: ClinGen
for review, treatable, metabolic tags were added to gene: OAT.
Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OAT were set to Gyrate atrophy of choroid and retina with or without ornithinemia MIM#258870
Review for gene: OAT was set to GREEN
Added comment: Rated as 'moderate actionability' in paediatric patients by ClinGen.

GA due to deficiency of the enzyme ornithine aminotransferase (OAT) is characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. GA first presents as night blindness and constriction of the visual field caused by sharply demarcated circular areas of chorioretinal atrophy in the periphery. Atrophic areas progressively increase, coalesce, and spread towards the macula leading to central visual loss and blindness (vision less than 20/200).

Age at diagnosis ranges from 1 month to 44 years. The condition is characterized by the development of chorioretinal atrophic patches that start in the mid-peripheral retina in the first decade of life. Myopia, night blindness, changes in the macula (including cystic changes), and visual field affection usually start in the first or second decade. Most patients with GA have posterior subcapsular cataracts by the end of the second decade. Irreversible loss of vision and blindness generally occurs between 40 and 55 years of age but is highly variable.

Treatment of GA consists mainly of dietary modifications to help lower elevated systemic ornithine levels. Restriction of dietary arginine, a precursor of ornithine, appears to have therapeutic value. Pediatric patients undergoing arginine restriction should receive enough calories in their diet supplemented by essential amino acids, vitamins, and minerals to avoid malnutrition and excessive break down of endogenous proteins.

A long-term observational study of 27 patients with GA, 17 who complied with the arginine-restricted diet and 10 who were noncompliant, found that at 14 years follow-up the rates of vision loss were significantly slower in the compliant group for 3 of the 4 outcome measures, when adjusted for age.
Sources: ClinGen
BabyScreen+ newborn screening v0.1752 PCSK9 Zornitza Stark Marked gene: PCSK9 as ready
BabyScreen+ newborn screening v0.1750 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489 to Carney complex, type 1, MIM# 160980
BabyScreen+ newborn screening v0.1749 PRKAR1A Zornitza Stark Classified gene: PRKAR1A as Green List (high evidence)
BabyScreen+ newborn screening v0.1749 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1748 PRKAR1A Zornitza Stark Tag for review tag was added to gene: PRKAR1A.
Tag cancer tag was added to gene: PRKAR1A.
Tag treatable tag was added to gene: PRKAR1A.
BabyScreen+ newborn screening v0.1748 PRKAR1A Zornitza Stark edited their review of gene: PRKAR1A: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen, principally due to benefit from early detection of cardiac myxomas through surveillance.

CNC is associated with skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas.

Lentigines are the most common presenting feature of CNC and may be present at birth. Typically, they increase in number at puberty, fade after the fourth decade, but may still be evident in the eighth decade. Cutaneous myxomas appear between birth and the fourth decade. Cardiac myxomas may occur at a young age. Breast myxomas occur in females after puberty. Males and females may develop nipple myxomas at any age. In a minority of individuals, PPNAD presents in the first two to three years; in the majority, it presents in the second or third decade. LCCSCT often present in the first decade. Signs and symptoms of CNC may be present at birth, but the median age of diagnosis is 20 years. Most patients with CNC present with a mild increase in GH. However, clinically evident acromegaly is a relatively frequent manifestation of CNC, occurring in approximately 10% of adults at the time of presentation. Most individuals with CNC have a normal life span. However, because some die at an early age, the average life expectancy for individuals with CNC is 50 years. Causes of death include complications of cardiac myxoma (myxoma emboli, cardiomyopathy, cardiac arrhythmia, and surgical intervention), metastatic or intracranial PMS, thyroid carcinoma, and metastatic pancreatic and testicular tumors.

The only preventive measure in an asymptomatic individual is surgical removal of a heart tumor (cardiac myxoma) prior to the development of heart dysfunction, stroke, or other embolism. Cardiac myxomas should be diagnosed early through regular screening.

Development of metabolic abnormalities from Cushing syndrome or arthropathy and other complications from acromegaly may be prevented by medical or surgical treatment of the respective endocrine manifestations.

The overall penetrance of CNC in those with a PRKAR1A pathogenic variant is greater than 95% by age 50 years. 30-60% have cardiac myxomas.; Changed rating: GREEN; Changed phenotypes: Carney complex, type 1, MIM# 160980
BabyScreen+ newborn screening v0.1748 RPS10 Zornitza Stark Marked gene: RPS10 as ready
BabyScreen+ newborn screening v0.1746 MEN1 Zornitza Stark changed review comment from: For review re age of onset: surveillance starts age 5, disease onset generally later.; to: For review re age of onset: surveillance starts age 5, disease onset generally later.

Rated as 'strong actionability' in paediatric patients by ClinGen.

Parathyroid tumors, which cause PHPT, are the most common feature and the first clinical manifestation in 90% of individuals with MEN1 with onset typically between ages 20 and 25 years. Almost all (95-100%) individuals with MEN1 can expect to have PHPT by age 50 years. However, MEN1 affects all age groups, with a reported age range of 5 to 81 years; 17% of MEN1 tumors are diagnosed under age 21. Untreated patients with MEN1 have a decreased life expectancy with a 50% probability of death by age 50. The cause of death in 50-70% of cases is due to a malignant tumor process or sequelae of the disease, with malignancies accounting for 30% of all deaths.
BabyScreen+ newborn screening v0.1746 SCN5A Zornitza Stark Marked gene: SCN5A as ready
BabyScreen+ newborn screening v0.1746 SCN5A Zornitza Stark Phenotypes for gene: SCN5A were changed from Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome; Brugada syndrome 1, MIM# 601144; Long QT syndrome 3 (MIM#603830); Long QT syndrome; Heart block, progressive, type IA, MIM# 113900 to Long QT syndrome 3 (MIM#603830); Brugada syndrome 1, MIM# 601144
BabyScreen+ newborn screening v0.1745 SCN5A Zornitza Stark Tag for review tag was added to gene: SCN5A.
Tag cardiac tag was added to gene: SCN5A.
Tag treatable tag was added to gene: SCN5A.
BabyScreen+ newborn screening v0.1745 SLC26A4 Zornitza Stark Phenotypes for gene: SLC26A4 were changed from Pendred syndrome, MIM #274600 to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600
BabyScreen+ newborn screening v0.1743 SLC26A4 Zornitza Stark reviewed gene: SLC26A4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791, Pendred syndrome 274600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1743 TGFB3 Zornitza Stark Marked gene: TGFB3 as ready
BabyScreen+ newborn screening v0.1743 TGFB3 Zornitza Stark Phenotypes for gene: TGFB3 were changed from Arrhythmogenic right ventricular dysplasia to Loeys-Dietz syndrome 5 , MIM#615582
BabyScreen+ newborn screening v0.1741 TGFB3 Zornitza Stark Tag for review tag was added to gene: TGFB3.
Tag cardiac tag was added to gene: TGFB3.
Tag treatable tag was added to gene: TGFB3.
BabyScreen+ newborn screening v0.1741 TGFB2 Zornitza Stark Marked gene: TGFB2 as ready
BabyScreen+ newborn screening v0.1740 TGFB2 Zornitza Stark Tag for review tag was added to gene: TGFB2.
Tag cardiac tag was added to gene: TGFB2.
Tag treatable tag was added to gene: TGFB2.
BabyScreen+ newborn screening v0.1740 TGFB2 Zornitza Stark gene: TGFB2 was added
gene: TGFB2 was added to gNBS. Sources: ClinGen
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4, MIM# 614816
Review for gene: TGFB2 was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms which are the major source of morbidity and mortality. Aortic growth can be faster than 10mm per year. Aortic dissection has been observed in early childhood, and the mean age of death is 26 years. Other life-threatening manifestations include spontaneous rupture of the spleen, bowel, and uterine rupture during pregnancy.

Prophylactic surgical repair is typically recommended at an aortic diameter of ≥ 4.2 cm.

Beta-blockers or other medications can be used to reduce hemodynamic stress.

Consider Medicalert bracelet.

Use of subacute bacterial endocarditis prophylaxis should be considered for individuals with connective tissue disorders and documented evidence of mitral and/or aortic regurgitation who are undergoing dental work or other procedures expected to contaminate the bloodstream with bacteria.

Because of a high risk of cervical spine instability, a flexion and extension x-ray of the cervical spine should be performed prior to intubation or any other procedure involving manipulation of the neck.
Sources: ClinGen
BabyScreen+ newborn screening v0.1739 TRDN Zornitza Stark Marked gene: TRDN as ready
BabyScreen+ newborn screening v0.1739 TRDN Zornitza Stark Phenotypes for gene: TRDN were changed from Catecholaminergic polymorphic ventricular tachycardia to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441
BabyScreen+ newborn screening v0.1737 TRDN Zornitza Stark Tag for review tag was added to gene: TRDN.
Tag cardiac tag was added to gene: TRDN.
Tag treatable tag was added to gene: TRDN.
BabyScreen+ newborn screening v0.1737 TRDN Zornitza Stark reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1737 TECRL Zornitza Stark Marked gene: TECRL as ready
BabyScreen+ newborn screening v0.1736 TECRL Zornitza Stark gene: TECRL was added
gene: TECRL was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: TECRL.
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Review for gene: TECRL was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1735 CALM3 Zornitza Stark Marked gene: CALM3 as ready
BabyScreen+ newborn screening v0.1734 CALM3 Zornitza Stark gene: CALM3 was added
gene: CALM3 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM3.
Mode of inheritance for gene: CALM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM3 were set to Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782
Penetrance for gene: CALM3 were set to Incomplete
Review for gene: CALM3 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1733 CALM2 Zornitza Stark Marked gene: CALM2 as ready
BabyScreen+ newborn screening v0.1732 CALM2 Zornitza Stark gene: CALM2 was added
gene: CALM2 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM2.
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM2 were set to Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Review for gene: CALM2 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1731 CALM1 Zornitza Stark Marked gene: CALM1 as ready
BabyScreen+ newborn screening v0.1730 CALM1 Zornitza Stark gene: CALM1 was added
gene: CALM1 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM1.
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM1 were set to Ventricular tachycardia, catecholaminergic polymorphic, 4, MIM# 614916
Penetrance for gene: CALM1 were set to Incomplete
Review for gene: CALM1 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1729 RPE65 Zornitza Stark Marked gene: RPE65 as ready
BabyScreen+ newborn screening v0.1728 RPE65 Zornitza Stark gene: RPE65 was added
gene: RPE65 was added to gNBS. Sources: ClinGen
for review, treatable, ophthalmological tags were added to gene: RPE65.
Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPE65 were set to Leber congenital amaurosis 2 MIM#204100; Retinitis pigmentosa 20 MIM#613794
Review for gene: RPE65 was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

Biallelic RPE65 mutation-associated retinal dystrophy is a form of IRD caused by biallelic pathogenic variants in RPE65; it presents as a spectrum of disease with variable age of onset and progression of vision loss. Common clinical findings across the spectrum include night blindness, progressive loss of visual fields and loss of central vision.

In LCA, night blindness often occurs from birth. Characteristically, these patients have residual cone-mediated vision in the first to third decades with progressive visual field loss until complete blindness is observed, most often in mid- to late-adulthood. A range of age of onset has been described for night blindness in RP, but it typically onsets in later childhood.

In December 2017, the FDA approved LUXTURNA (voretigene neparvovec-rzyl) gene therapy for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The FDA’s conclusion of efficacy is based on improvement in a functional vision score over 1 year in a single open-label controlled Phase 3 study of 31 affected patients. The average age of the 31 randomized patients was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). Functional vision was scored by a patient’s ability to navigate a course in various luminance levels. Using both treated eyes of the 21 subjects in the LUXTURNA treatment group, 11 (52%) had a clinically meaningful score improvement, while only one of the ten (10%) subjects in the control group had a clinically meaningful score improvement. Using the first treated eye only, 15/21 (71%) had a clinically meaningful score improvement, while no comparable score improvement was observed in controls. Other secondary clinical outcomes were also examined. Analysis of white light full-field light sensitivity threshold testing showed statistically significant improvement at 1 year in the LUXTURNA treatment group compared to the control group. The change in visual acuity was not significantly different between the LUXTURNA and control groups.

LUXTURNA is administered subretinally by injection. Per the FDA package insert, the most common adverse reactions (incidence ≥ 5%) in the clinical trials for LUXTURNA included conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), and macular hole. Several other ocular adverse effects were also reported, including risk of endophthalmitis. Safety data was included on the basis of 41 patients (81 eyes).

For review: availability of therapy?
Sources: ClinGen
BabyScreen+ newborn screening v0.1727 CP Zornitza Stark Marked gene: CP as ready
BabyScreen+ newborn screening v0.1726 WT1 Zornitza Stark Marked gene: WT1 as ready
BabyScreen+ newborn screening v0.1725 ITGB3 Zornitza Stark Marked gene: ITGB3 as ready
BabyScreen+ newborn screening v0.1724 ITGB3 Zornitza Stark gene: ITGB3 was added
gene: ITGB3 was added to gNBS. Sources: ClinGen
treatable, haematological tags were added to gene: ITGB3.
Mode of inheritance for gene: ITGB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGB3 were set to Glanzmann thrombasthenia 2, MIM# 619267
Review for gene: ITGB3 was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long.

Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.

The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.

Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting.
Sources: ClinGen
BabyScreen+ newborn screening v0.1723 ITGA2B Zornitza Stark Marked gene: ITGA2B as ready
BabyScreen+ newborn screening v0.1722 ITGA2B Zornitza Stark gene: ITGA2B was added
gene: ITGA2B was added to gNBS. Sources: ClinGen
treatable, haematological tags were added to gene: ITGA2B.
Mode of inheritance for gene: ITGA2B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGA2B were set to Glanzmann thrombasthaenia 1, MIM# 273800
Review for gene: ITGA2B was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long.

Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.

The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.

Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting.
Sources: ClinGen
BabyScreen+ newborn screening v0.1721 F7 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity.

Treatment: Recombinant coagulation Factor VIIa

Non-genetic confirmatory testing: factor VII level; to: Well established gene-disease association.

Variable severity.

Treatment: Recombinant coagulation Factor VIIa

Non-genetic confirmatory testing: factor VII level

Rated as 'strong actionability' in paediatric patients by ClinGen.

Clinical expression of factor VII deficiency is highly variable, and no consistent relationship has been found between the severity of the hemorrhagic syndrome and the residual levels of FVII activity. Individuals can be completely asymptomatic despite a very low FVII level. A bleeding history appears more predictive of further bleeding than the factor VII level. Factor VII levels increase during pregnancy, but levels usually remain insufficient for hemostasis in severely affected cases. Individuals with no history of bleeding do not appear to be at increased risk of PPH. Heterozygotes often have approximately half-normal levels of coagulation factors and are often asymptomatic. However, up to 2% of patients with severe bleeding phenotype are heterozygotes.

Consider prophylaxis using rFVIIa in certain circumstances. Long term prophylaxis should be considered for cases with a personal or family history of severe bleeding or with FVII activity <0.01 IU/ml using rFVIIa, adjusting to maintain clinical response. Short term prophylaxis should be considered for cases for neonates without a personal or family history of severe bleeding but who have FVII activity 0.01-0.05 IU/ml up to 6-12 months of age.
BabyScreen+ newborn screening v0.1721 ABCC8 Zornitza Stark Marked gene: ABCC8 as ready
BabyScreen+ newborn screening v0.1721 COL9A1 Zornitza Stark Marked gene: COL9A1 as ready
BabyScreen+ newborn screening v0.1721 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
BabyScreen+ newborn screening v0.1721 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from Char syndrome to Char syndrome, MIM 169100
BabyScreen+ newborn screening v0.1719 TFAP2B Zornitza Stark reviewed gene: TFAP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Char syndrome, MIM 169100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1719 TFAP2A Zornitza Stark Marked gene: TFAP2A as ready
BabyScreen+ newborn screening v0.1717 TECTA Zornitza Stark Marked gene: TECTA as ready
BabyScreen+ newborn screening v0.1714 STAR Zornitza Stark Tag treatable tag was added to gene: STAR.
Tag endocrine tag was added to gene: STAR.
BabyScreen+ newborn screening v0.1712 RET Zornitza Stark Marked gene: RET as ready
BabyScreen+ newborn screening v0.1712 PSPH Zornitza Stark Marked gene: PSPH as ready
BabyScreen+ newborn screening v0.1710 MMADHC Zornitza Stark Marked gene: MMADHC as ready
BabyScreen+ newborn screening v0.1710 MARVELD2 Zornitza Stark Tag deafness tag was added to gene: MARVELD2.
BabyScreen+ newborn screening v0.1710 TFAP2B David Amor reviewed gene: TFAP2B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: MIM 169100 Char syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1710 COL9A1 David Amor changed review comment from: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment.

Severity: moderate-severe

Age of onset: congenital

Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia

Treatment: as per other Stickler syndrome; to: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment.

Severity: moderate-severe

Age of onset: congenital

Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia

Treatment: as per other Stickler syndrome
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor commented on gene: ABCC8: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor commented on gene: ABCC8: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor changed review comment from: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.



Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
; to: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor changed review comment from: Gene-disease association: strong. Note sporadic cases with focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes, glucose, insulin, free fatty acid levels

Treatment: as per rx-genes, Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus; to: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.



Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 L1CAM Zornitza Stark Marked gene: L1CAM as ready
BabyScreen+ newborn screening v0.1708 KCNJ11 Zornitza Stark changed review comment from: Association with hyperinsulinism is well established.

Onset is congenital.

Treatment: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

Association with neonatal diabetes is also well established.

Treatment: Insulin, glibenclamide, oral pancreatic enzymes.

Phenotypes are expected to be distinguishable clinically.; to: Association with hyperinsulinism is well established, mono-allelic variants.

Onset is congenital.

Treatment: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

Association with neonatal diabetes is also well established, bi-allelic variants.

Treatment: Insulin, glibenclamide, oral pancreatic enzymes.

Phenotypes are expected to be distinguishable clinically.
BabyScreen+ newborn screening v0.1708 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
BabyScreen+ newborn screening v0.1706 GNS Zornitza Stark Marked gene: GNS as ready
BabyScreen+ newborn screening v0.1706 GNS Zornitza Stark Phenotypes for gene: GNS were changed from Mucopolysaccharidosis IIId to Mucopolysaccharidosis type IIID, MIM# 252940
BabyScreen+ newborn screening v0.1702 GNAS Zornitza Stark Marked gene: GNAS as ready
BabyScreen+ newborn screening v0.1702 GNAS Zornitza Stark reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoparathyroidism Ia, MIM#103580 (Hypothyroidism); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
BabyScreen+ newborn screening v0.1702 GLRA1 Zornitza Stark Marked gene: GLRA1 as ready
BabyScreen+ newborn screening v0.1701 GLA Zornitza Stark changed review comment from: For review: screen only for males or include both?; to: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started.
BabyScreen+ newborn screening v0.1701 GJB2 Zornitza Stark Marked gene: GJB2 as ready
BabyScreen+ newborn screening v0.1701 GJB2 Zornitza Stark Phenotypes for gene: GJB2 were changed from Deafness and palmoplantar keratoderma; Deafness to Deafness, autosomal recessive 1A, MIM# 220290
BabyScreen+ newborn screening v0.1699 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429 to Neonatal diabetes mellitus, MONDO:0016391, GATA4-related
BabyScreen+ newborn screening v0.1698 F9 Zornitza Stark Marked gene: F9 as ready
BabyScreen+ newborn screening v0.1698 F8 Zornitza Stark Marked gene: F8 as ready
BabyScreen+ newborn screening v0.1698 F7 Zornitza Stark Marked gene: F7 as ready
BabyScreen+ newborn screening v0.1698 FGF23 Zornitza Stark Marked gene: FGF23 as ready
BabyScreen+ newborn screening v0.1697 FGF23 Zornitza Stark gene: FGF23 was added
gene: FGF23 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: FGF23 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: FGF23 were set to autosomal dominant hypophosphatemic rickets MONDO:0008660; familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome MONDO:0100251
Review for gene: FGF23 was set to GREEN
Added comment: Mono-allelic GoF variants are associated with hypophosphataemic rickets.

Onset in some is in infancy (others adolescence).

Treatment: phosphate supplementation and calcitriol

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase levels, urine calcium level

Bi-allelic LoF variants are associated with tumoral calcinosis.

Age of onset and severity are variable, but include early childhood.

Treatment: dietary restriction, antacids, phosphate binders, acetazolamide, hemodialysis

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase, vitamin D serum levels, urine calcium, phosphate levels, plasma levels of the C-terminal portion of the phosphate-regulating hormone, fibroblast growth factor 23
Sources: Expert list
BabyScreen+ newborn screening v0.1696 F5 Zornitza Stark Marked gene: F5 as ready
BabyScreen+ newborn screening v0.1694 F2 Zornitza Stark Marked gene: F2 as ready
BabyScreen+ newborn screening v0.1691 F13A1 Zornitza Stark Marked gene: F13A1 as ready
BabyScreen+ newborn screening v0.1691 F11 Zornitza Stark Marked gene: F11 as ready
BabyScreen+ newborn screening v0.1688 ENPP1 Zornitza Stark Tag endocrine tag was added to gene: ENPP1.
Tag vascular tag was added to gene: ENPP1.
BabyScreen+ newborn screening v0.1688 ENG Zornitza Stark Tag treatable tag was added to gene: ENG.
Tag vascular tag was added to gene: ENG.
BabyScreen+ newborn screening v0.1687 CASR Zornitza Stark Marked gene: CASR as ready
BabyScreen+ newborn screening v0.1687 CASR Zornitza Stark Phenotypes for gene: CASR were changed from Hyperparathyroidism, neonatal, MIM# 239200 to Hypocalcemia, autosomal dominant MIM#601198; Hyperparathyroidism, neonatal MIM#239200
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark changed review comment from: AD hypoCa: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.; to: AD hypoCa: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.

AD/AR hyperparathyroidism: established gene-disease association.

Congenital onset.

Treatment: bisphosphonate, parathyroidectomy, cinacalcet

Non-genetic confirmatory testing: Ca, PTH.
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark changed review comment from: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.; to: AD hypoCa: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark edited their review of gene: CASR: Changed phenotypes: Hypocalcemia, autosomal dominant MIM#601198, Hyperparathyroidism, neonatal MIM#239200
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark edited their review of gene: CASR: Changed phenotypes: Hypocalciuric hypercalcemia, type I, MIM# 145980, Hyperparathyroidism, neonatal MIM#239200
BabyScreen+ newborn screening v0.1684 CASR Zornitza Stark changed review comment from: Treatment: Thiazide diuretics, calcium, calcitriol; to: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.
BabyScreen+ newborn screening v0.1684 COL4A3 Zornitza Stark Marked gene: COL4A3 as ready
BabyScreen+ newborn screening v0.1682 COL4A4 Zornitza Stark Marked gene: COL4A4 as ready
BabyScreen+ newborn screening v0.1681 COL4A4 Zornitza Stark changed review comment from: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.; to: Well established gene-disease association.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.
BabyScreen+ newborn screening v0.1681 COL4A4 Zornitza Stark changed review comment from: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.; to: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.
BabyScreen+ newborn screening v0.1681 COL4A5 Zornitza Stark changed review comment from: Well established gene-disease association.

Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.

For review: screen both males and females?; to: Well established gene-disease association.

Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.
BabyScreen+ newborn screening v0.1681 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
BabyScreen+ newborn screening v0.1681 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from Ehlers-Danlos syndrome, type IV to Ehlers-Danlos syndrome, vascular type, MIM# 130050
BabyScreen+ newborn screening v0.1679 COL3A1 Zornitza Stark Tag for review tag was added to gene: COL3A1.
Tag cardiac tag was added to gene: COL3A1.
BabyScreen+ newborn screening v0.1679 COL3A1 Zornitza Stark reviewed gene: COL3A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, vascular type, MIM# 130050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1679 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
BabyScreen+ newborn screening v0.1677 CDAN1 Zornitza Stark Marked gene: CDAN1 as ready
BabyScreen+ newborn screening v0.1675 CARD11 Zornitza Stark Tag treatable tag was added to gene: CARD11.
Tag immunological tag was added to gene: CARD11.
BabyScreen+ newborn screening v0.1675 UROS John Christodoulou reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30685241; Phenotypes: hydros, photosensitivity, erythrodontia, corneal scarring, haemolytic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1675 TRMU John Christodoulou reviewed gene: TRMU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33485800, PMID: 33365252; Phenotypes: liver failure, Leigh syndrome, cardiomyopathy' myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1675 TFG Zornitza Stark Marked gene: TFG as ready
BabyScreen+ newborn screening v0.1675 TFG Zornitza Stark Phenotypes for gene: TFG were changed from Hereditary motor and sensory neuropathy to Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484; Spastic paraplegia 57, autosomal recessive, MIM# 615658
BabyScreen+ newborn screening v0.1672 TFG Zornitza Stark reviewed gene: TFG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484, Spastic paraplegia 57, autosomal recessive, MIM# 615658; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1672 TG Zornitza Stark Marked gene: TG as ready
BabyScreen+ newborn screening v0.1670 TGM5 Zornitza Stark Marked gene: TGM5 as ready
BabyScreen+ newborn screening v0.1668 TGM1 Zornitza Stark Marked gene: TGM1 as ready
BabyScreen+ newborn screening v0.1666 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
BabyScreen+ newborn screening v0.1665 TGFBR2 Zornitza Stark Tag cardiac tag was added to gene: TGFBR2.
Tag treatable tag was added to gene: TGFBR2.
BabyScreen+ newborn screening v0.1665 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
BabyScreen+ newborn screening v0.1664 TGFBR1 Zornitza Stark Tag cardiac tag was added to gene: TGFBR1.
Tag treatable tag was added to gene: TGFBR1.
BabyScreen+ newborn screening v0.1664 TH Zornitza Stark Marked gene: TH as ready
BabyScreen+ newborn screening v0.1663 THRA Zornitza Stark Marked gene: THRA as ready
BabyScreen+ newborn screening v0.1661 THRB Zornitza Stark Marked gene: THRB as ready
BabyScreen+ newborn screening v0.1661 THRB Zornitza Stark Phenotypes for gene: THRB were changed from Thyroid hormone resistance to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
BabyScreen+ newborn screening v0.1658 THRB Zornitza Stark reviewed gene: THRB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid hormone resistance, MIM# 188570, Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, selective pituitary, MIM# 145650; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1658 TIMM8A Zornitza Stark Marked gene: TIMM8A as ready
BabyScreen+ newborn screening v0.1654 TK2 Zornitza Stark Marked gene: TK2 as ready
BabyScreen+ newborn screening v0.1653 TMC1 Zornitza Stark Marked gene: TMC1 as ready
BabyScreen+ newborn screening v0.1651 TMEM43 Zornitza Stark Marked gene: TMEM43 as ready
BabyScreen+ newborn screening v0.1651 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from Arrhythmogenic right ventricular dysplasia 5 to Arrhythmogenic right ventricular dysplasia 5 MIM#604400
BabyScreen+ newborn screening v0.1648 TMEM67 Zornitza Stark Marked gene: TMEM67 as ready
BabyScreen+ newborn screening v0.1645 TMIE Zornitza Stark Marked gene: TMIE as ready
BabyScreen+ newborn screening v0.1645 TK2 John Christodoulou reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29602790, PMID: 31125140, PMID: 23385875; Phenotypes: myopathy, ophthalmoparesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1643 THRA John Christodoulou changed review comment from: Congenital nongoitrous hypothyroidism 6

normal TSH, so will be missed by NBS

treatment with thyroxine; to: Congenital nongoitrous hypothyroidism 6

normal TSH, so will be missed by NBS

treatment with thyroxine; others report that patients are resistant to thyroxine therapy (PMID: 28527577)
BabyScreen+ newborn screening v0.1643 TH John Christodoulou reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301610; Phenotypes: dystonia, Parkinsonism, dev delay, hypotonia, oculogyric crises; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1643 UROS Zornitza Stark Marked gene: UROS as ready
BabyScreen+ newborn screening v0.1641 USH1C Zornitza Stark Marked gene: USH1C as ready
BabyScreen+ newborn screening v0.1639 USH1G Zornitza Stark Marked gene: USH1G as ready
BabyScreen+ newborn screening v0.1637 USH2A Zornitza Stark Marked gene: USH2A as ready
BabyScreen+ newborn screening v0.1635 VCAN Zornitza Stark Marked gene: VCAN as ready
BabyScreen+ newborn screening v0.1632 TCN2 John Christodoulou reviewed gene: TCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32841161, PMID: 33685478; Phenotypes: failure to thrive, megaloblastic anaemia, recurrent infections, ID, vomiting, diarrhoea; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1632 ARSB Zornitza Stark Tag metabolic tag was added to gene: ARSB.
BabyScreen+ newborn screening v0.1632 ARSA Zornitza Stark Tag metabolic tag was added to gene: ARSA.
BabyScreen+ newborn screening v0.1632 ARPC1B Zornitza Stark Tag immunological tag was added to gene: ARPC1B.
BabyScreen+ newborn screening v0.1632 ARG1 Zornitza Stark Tag metabolic tag was added to gene: ARG1.
BabyScreen+ newborn screening v0.1632 ACVRL1 Zornitza Stark Tag treatable tag was added to gene: ACVRL1.
Tag vascular tag was added to gene: ACVRL1.
BabyScreen+ newborn screening v0.1632 PROS1 Zornitza Stark Marked gene: PROS1 as ready
BabyScreen+ newborn screening v0.1629 PROP1 Zornitza Stark Marked gene: PROP1 as ready
BabyScreen+ newborn screening v0.1629 PROP1 Zornitza Stark reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 2 (MIM#262600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1629 PROKR2 Zornitza Stark Marked gene: PROKR2 as ready
BabyScreen+ newborn screening v0.1626 PROC Zornitza Stark Marked gene: PROC as ready
BabyScreen+ newborn screening v0.1623 PRKDC Zornitza Stark Marked gene: PRKDC as ready
BabyScreen+ newborn screening v0.1623 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
BabyScreen+ newborn screening v0.1623 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1623 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from Carney complex to Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489
BabyScreen+ newborn screening v0.1622 PRKAR1A Zornitza Stark Classified gene: PRKAR1A as Red List (low evidence)
BabyScreen+ newborn screening v0.1622 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1621 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800, Carney complex, type 1, MIM# 160980, Myxoma, intracardiac, MIM# 255960, Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark Marked gene: PRF1 as ready
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark changed review comment from: Treatment: Emapalumab, bone marrow transplant; to: Well established gene-disease association.

Onset is generally in infancy or early childhood.

Treatment: Emapalumab, bone marrow transplant.

Non-genetic confirmatory tests: natural killer cell activity, cytotoxic T lymphocyte activity
BabyScreen+ newborn screening v0.1621 PNPO Zornitza Stark Marked gene: PNPO as ready
BabyScreen+ newborn screening v0.1619 PPT1 Zornitza Stark Marked gene: PPT1 as ready
BabyScreen+ newborn screening v0.1616 POU4F3 Zornitza Stark Marked gene: POU4F3 as ready
BabyScreen+ newborn screening v0.1614 POU3F4 Zornitza Stark Marked gene: POU3F4 as ready
BabyScreen+ newborn screening v0.1612 PYGL John Christodoulou edited their review of gene: PYGL: Changed publications: PMID: 30659246, PMID: 35725468, PMID: 20301760; Changed phenotypes: hepatomegaly, hypoglycaemia, cardiomyopathy, short stature
BabyScreen+ newborn screening v0.1612 POU1F1 Zornitza Stark Marked gene: POU1F1 as ready
BabyScreen+ newborn screening v0.1612 POU1F1 Zornitza Stark Phenotypes for gene: POU1F1 were changed from Pituitary hormone deficiency, MIM#613038 to Pituitary hormone deficiency, combined, 1 MIM# 613038
BabyScreen+ newborn screening v0.1610 POU1F1 Zornitza Stark reviewed gene: POU1F1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 1 MIM# 613038; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1610 PYGL John Christodoulou commented on gene: PYGL: Generally a mild disorder - presenting in early childhood with hepatomegaly due to glycogen storage

some at risk of hypoglycaemia; some may develop muscle cramps or cardiomyopathy

risk of hepatic adenomas - ultrasound surveillance recommended from 5 yrs

treatment cornstarch and high protein diet - growth improves and hypoglycaemia is no longer problem
BabyScreen+ newborn screening v0.1610 PYGL John Christodoulou reviewed gene: PYGL: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: hepatomegaly, hypoglycaemia, cardiomyo; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1610 PORCN Zornitza Stark Marked gene: PORCN as ready
BabyScreen+ newborn screening v0.1607 POR Zornitza Stark Marked gene: POR as ready
BabyScreen+ newborn screening v0.1606 POMT2 Zornitza Stark Marked gene: POMT2 as ready
BabyScreen+ newborn screening v0.1606 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 MIM# 613158
BabyScreen+ newborn screening v0.1604 POMT2 Zornitza Stark reviewed gene: POMT2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1604 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
BabyScreen+ newborn screening v0.1604 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135; Retinitis pigmentosa 76, MIM# 617123
BabyScreen+ newborn screening v0.1602 POMGNT1 Zornitza Stark reviewed gene: POMGNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135, Retinitis pigmentosa 76 617123; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1602 POLH Zornitza Stark Marked gene: POLH as ready
BabyScreen+ newborn screening v0.1602 POLH Zornitza Stark Phenotypes for gene: POLH were changed from Xeroderma pigmentosum to Xeroderma pigmentosum, variant type, MIM# 278750
BabyScreen+ newborn screening v0.1600 POLH Zornitza Stark reviewed gene: POLH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, variant type, MIM# 278750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1600 POLG Zornitza Stark Marked gene: POLG as ready
BabyScreen+ newborn screening v0.1596 PNKP Zornitza Stark Marked gene: PNKP as ready
BabyScreen+ newborn screening v0.1593 POMT1 Zornitza Stark Marked gene: POMT1 as ready
BabyScreen+ newborn screening v0.1593 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1; Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308
BabyScreen+ newborn screening v0.1591 POMT1 Zornitza Stark reviewed gene: POMT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1591 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
BabyScreen+ newborn screening v0.1591 PQBP1 Zornitza Stark Phenotypes for gene: PQBP1 were changed from Mental retardation to Renpenning syndrome, MIM#309500
BabyScreen+ newborn screening v0.1589 PNKD Zornitza Stark Marked gene: PNKD as ready
BabyScreen+ newborn screening v0.1589 PNKD Zornitza Stark Phenotypes for gene: PNKD were changed from Paroxysmal nonkinesiogenic dyskinesia to Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800
BabyScreen+ newborn screening v0.1587 PNKD Zornitza Stark reviewed gene: PNKD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1587 PMP22 Zornitza Stark Marked gene: PMP22 as ready
BabyScreen+ newborn screening v0.1587 PMP22 Zornitza Stark Phenotypes for gene: PMP22 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 1A, MIM# 118220; Charcot-Marie-Tooth disease, type 1E, MIM# 118300; Dejerine-Sottas disease, MIM# 145900; Neuropathy, recurrent, with pressure palsies 162500; Roussy-Levy syndrome 180800
BabyScreen+ newborn screening v0.1585 PMP22 Zornitza Stark reviewed gene: PMP22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 1A, MIM# 118220, Charcot-Marie-Tooth disease, type 1E, MIM# 118300, Dejerine-Sottas disease, MIM# 145900, Neuropathy, recurrent, with pressure palsies 162500, Roussy-Levy syndrome 180800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1585 PMM2 Zornitza Stark Marked gene: PMM2 as ready
BabyScreen+ newborn screening v0.1582 PLPBP Zornitza Stark Marked gene: PLPBP as ready
BabyScreen+ newborn screening v0.1581 PLPBP Zornitza Stark reviewed gene: PLPBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30668673; Phenotypes: Epilepsy, early-onset, vitamin B6-dependent, MIM#617290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1581 PLP1 Zornitza Stark Marked gene: PLP1 as ready
BabyScreen+ newborn screening v0.1581 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from Pelizaeus-Merzbacher disease; Spastic paraplegia 2, X-linked to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
BabyScreen+ newborn screening v0.1579 PLP1 Zornitza Stark reviewed gene: PLP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1579 PLOD1 Zornitza Stark Marked gene: PLOD1 as ready
BabyScreen+ newborn screening v0.1577 PLG Zornitza Stark Marked gene: PLG as ready
BabyScreen+ newborn screening v0.1577 PLG Zornitza Stark Phenotypes for gene: PLG were changed from Hereditary angioedema-4 (HAE4), MIM#619360; Plasminogen deficiency, type I, MIM# 217090 to Plasminogen deficiency, type I, MIM# 217090
BabyScreen+ newborn screening v0.1576 PLEC Zornitza Stark Marked gene: PLEC as ready
BabyScreen+ newborn screening v0.1576 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from Muscular dystrophy; Epidermolysis bullosa simplex to Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723
BabyScreen+ newborn screening v0.1573 PLEC Zornitza Stark reviewed gene: PLEC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670, Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138, Epidermolysis bullosa simplex, Ogna type MIM#131950, Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1573 PLCE1 Zornitza Stark Marked gene: PLCE1 as ready
BabyScreen+ newborn screening v0.1571 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
BabyScreen+ newborn screening v0.1571 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1 to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953
BabyScreen+ newborn screening v0.1569 PLA2G6 Zornitza Stark reviewed gene: PLA2G6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile neuroaxonal dystrophy 1 MIM#256600, Neurodegeneration with brain iron accumulation 2B MIM#610217, Parkinson disease 14, autosomal recessive MIM#612953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1569 PKLR Zornitza Stark Marked gene: PKLR as ready
BabyScreen+ newborn screening v0.1568 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
BabyScreen+ newborn screening v0.1566 PKD2 Zornitza Stark Marked gene: PKD2 as ready
BabyScreen+ newborn screening v0.1564 PKD2 Zornitza Stark changed review comment from: Well established gene-disease association.

Onset of renal failure is generally in adulthood, though cysts are apparent earlier.

Treatment: Tolvaptan; to: Well established gene-disease association.

Onset of renal failure is generally in late adulthood, though cysts are apparent earlier.

Treatment: Tolvaptan
BabyScreen+ newborn screening v0.1564 PKD1 Zornitza Stark Marked gene: PKD1 as ready
BabyScreen+ newborn screening v0.1562 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
BabyScreen+ newborn screening v0.1561 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3CA were set to 33392635; 33639990
Phenotypes for gene: PIK3CA were set to PIK3CA related overgrowth spectrum
Review for gene: PIK3CA was set to AMBER
Added comment: Established association with a range of overgrowth phenotypes.

Note variants are SOMATIC and may not be detectable reliably.

Treatment: alpelisib, miransertib. Unsure if these are available.
Sources: Expert list
BabyScreen+ newborn screening v0.1560 PINK1 Zornitza Stark Marked gene: PINK1 as ready
BabyScreen+ newborn screening v0.1560 PINK1 Zornitza Stark Phenotypes for gene: PINK1 were changed from Parkinson disease 6, early onset to Parkinson disease 6, early onset, MIM#605909
BabyScreen+ newborn screening v0.1557 PINK1 Zornitza Stark reviewed gene: PINK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease 6, early onset, MIM#605909; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1557 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
BabyScreen+ newborn screening v0.1556 PIK3CD Zornitza Stark Marked gene: PIK3CD as ready
BabyScreen+ newborn screening v0.1553 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
BabyScreen+ newborn screening v0.1553 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Arthrogryposis, distal, type 5 to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145); Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146
BabyScreen+ newborn screening v0.1550 PIEZO2 Zornitza Stark reviewed gene: PIEZO2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145), Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1550 PDZD7 Zornitza Stark Marked gene: PDZD7 as ready
BabyScreen+ newborn screening v0.1549 PHF6 Zornitza Stark Marked gene: PHF6 as ready
BabyScreen+ newborn screening v0.1547 PHEX Zornitza Stark Marked gene: PHEX as ready
BabyScreen+ newborn screening v0.1545 PGM3 Zornitza Stark Marked gene: PGM3 as ready
BabyScreen+ newborn screening v0.1545 TCOF1 Seb Lunke Marked gene: TCOF1 as ready
BabyScreen+ newborn screening v0.1543 TCN2 Seb Lunke Marked gene: TCN2 as ready
BabyScreen+ newborn screening v0.1542 TCIRG1 Seb Lunke Marked gene: TCIRG1 as ready
BabyScreen+ newborn screening v0.1541 TCF3 Seb Lunke Marked gene: TCF3 as ready
BabyScreen+ newborn screening v0.1539 TBX5 Seb Lunke Marked gene: TBX5 as ready
BabyScreen+ newborn screening v0.1537 TBX19 Seb Lunke Marked gene: TBX19 as ready
BabyScreen+ newborn screening v0.1536 TBX1 Seb Lunke Marked gene: TBX1 as ready
BabyScreen+ newborn screening v0.1536 TBX1 Seb Lunke Phenotypes for gene: TBX1 were changed from DiGeorge syndrome to DiGeorge syndrome MIM# 188400; Velocardiofacial syndrome MIM# 192430
BabyScreen+ newborn screening v0.1534 TBX1 Seb Lunke Tag for review tag was added to gene: TBX1.
Tag cardiac tag was added to gene: TBX1.
Tag immunological tag was added to gene: TBX1.
BabyScreen+ newborn screening v0.1534 TBX1 Seb Lunke reviewed gene: TBX1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: DiGeorge syndrome MIM# 188400, Velocardiofacial syndrome MIM# 192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1534 TBC1D24 Seb Lunke Marked gene: TBC1D24 as ready
BabyScreen+ newborn screening v0.1534 TBC1D24 Seb Lunke Phenotypes for gene: TBC1D24 were changed from Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome to DOORS syndrome MIM#220500
BabyScreen+ newborn screening v0.1532 TAZ Seb Lunke Marked gene: TAZ as ready
BabyScreen+ newborn screening v0.1531 TAZ Seb Lunke reviewed gene: TAZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1530 TAZ Seb Lunke reviewed gene: TAZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1530 SURF1 Seb Lunke Marked gene: SURF1 as ready
BabyScreen+ newborn screening v0.1530 SURF1 Seb Lunke Phenotypes for gene: SURF1 were changed from Leigh syndrome, due to COX deficiency to Charcot-Marie-Tooth disease, type 4K MIM#616684; Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110
BabyScreen+ newborn screening v0.1528 SURF1 Seb Lunke reviewed gene: SURF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4K MIM#616684, Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1528 SUOX Seb Lunke Marked gene: SUOX as ready
BabyScreen+ newborn screening v0.1526 SUCLG1 Seb Lunke Marked gene: SUCLG1 as ready
BabyScreen+ newborn screening v0.1524 SUCLA2 Seb Lunke Marked gene: SUCLA2 as ready
BabyScreen+ newborn screening v0.1522 STXBP2 Seb Lunke Marked gene: STXBP2 as ready
BabyScreen+ newborn screening v0.1521 STXBP2 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant

Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity; to: Established gene-disease association.

Childhood onset, hyperinflammatory disorder

Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant

Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity
BabyScreen+ newborn screening v0.1521 STXBP1 Seb Lunke Marked gene: STXBP1 as ready
BabyScreen+ newborn screening v0.1521 STXBP1 Seb Lunke Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile to Developmental and epileptic encephalopathy 4, MIM# 612164
BabyScreen+ newborn screening v0.1519 STX11 Seb Lunke Marked gene: STX11 as ready
BabyScreen+ newborn screening v0.1519 STS Seb Lunke Marked gene: STS as ready
BabyScreen+ newborn screening v0.1517 TMEM43 Lilian Downie reviewed gene: TMEM43: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301310, PMID: 34674311; Phenotypes: Arrhythmogenic right ventricular dysplasia 5 MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1517 STRC Seb Lunke Marked gene: STRC as ready
BabyScreen+ newborn screening v0.1515 STRA6 Seb Lunke Marked gene: STRA6 as ready
BabyScreen+ newborn screening v0.1513 STK11 Seb Lunke Marked gene: STK11 as ready
BabyScreen+ newborn screening v0.1510 STAT3 Seb Lunke Marked gene: STAT3 as ready
BabyScreen+ newborn screening v0.1509 STAR Seb Lunke Marked gene: STAR as ready
BabyScreen+ newborn screening v0.1509 STAR Seb Lunke Gene: star has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1509 STAR Seb Lunke Phenotypes for gene: STAR were changed from Congenital lipoid adrenal hyperplasia, MIM#201710 to Congenital lipoid adrenal hyperplasia, MIM#201710
BabyScreen+ newborn screening v0.1508 STAR Seb Lunke reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1508 STAC3 Seb Lunke Marked gene: STAC3 as ready
BabyScreen+ newborn screening v0.1507 SRP54 Seb Lunke Marked gene: SRP54 as ready
BabyScreen+ newborn screening v0.1507 SRCAP Seb Lunke Marked gene: SRCAP as ready
BabyScreen+ newborn screening v0.1507 SRCAP Seb Lunke Phenotypes for gene: SRCAP were changed from Floating-Harbor syndrome to Floating-Harbor syndrome MIM#136140; Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, MIM# 619595
BabyScreen+ newborn screening v0.1505 SRCAP Seb Lunke reviewed gene: SRCAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Floating-Harbor syndrome MIM#136140, Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, MIM# 619595; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1505 SPTLC1 Seb Lunke Marked gene: SPTLC1 as ready
BabyScreen+ newborn screening v0.1505 SPTLC1 Seb Lunke Phenotypes for gene: SPTLC1 were changed from Neuropathy, hereditary sensory and autonomic, type IA to Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400
BabyScreen+ newborn screening v0.1503 SPTLC1 Seb Lunke reviewed gene: SPTLC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1503 PRX Zornitza Stark Marked gene: PRX as ready
BabyScreen+ newborn screening v0.1503 PRX Zornitza Stark Phenotypes for gene: PRX were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 4F, MIM# 614895; Dejerine-Sottas disease, MIM# 145900
BabyScreen+ newborn screening v0.1501 PRX Zornitza Stark reviewed gene: PRX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4F, MIM# 614895, Dejerine-Sottas disease, MIM# 145900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1501 PSAP Zornitza Stark Marked gene: PSAP as ready
BabyScreen+ newborn screening v0.1501 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from Metachromatic leukodystrophy to Parkinson disease; Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900; Gaucher disease, atypical, MIM# 610539
BabyScreen+ newborn screening v0.1498 PSAP Zornitza Stark reviewed gene: PSAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease, Combined SAP deficiency, MIM# 611721, Encephalopathy due to prosaposin deficiency, MONDO:0012719, Krabbe disease, atypical, MIM# 611722, Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, Gaucher disease, atypical, MIM# 610539; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1498 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
BabyScreen+ newborn screening v0.1498 PTCH1 Zornitza Stark Phenotypes for gene: PTCH1 were changed from Nevoid basal cell carcinoma syndrome to Basal cell nevus syndrome, MIM# 109400
BabyScreen+ newborn screening v0.1496 PTEN Zornitza Stark Marked gene: PTEN as ready
BabyScreen+ newborn screening v0.1494 PTF1A Zornitza Stark Marked gene: PTF1A as ready
BabyScreen+ newborn screening v0.1494 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pancreatic agenesis 2, MIM# 615935, Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1494 PTH1R Zornitza Stark Marked gene: PTH1R as ready
BabyScreen+ newborn screening v0.1494 PTH1R Zornitza Stark Phenotypes for gene: PTH1R were changed from Metaphyseal chondrodysplasia to Failure of tooth eruption, primary MIM#125350; Eiken syndrome MIM#600002; Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400; Chondrodysplasia, Blomstrand type MIM#215045
BabyScreen+ newborn screening v0.1491 PTH1R Zornitza Stark reviewed gene: PTH1R: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Failure of tooth eruption, primary MIM#125350, Eiken syndrome MIM#600002, Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400, Chondrodysplasia, Blomstrand type MIM#215045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1491 PTPRC Zornitza Stark Marked gene: PTPRC as ready
BabyScreen+ newborn screening v0.1491 PYGL Zornitza Stark Marked gene: PYGL as ready
BabyScreen+ newborn screening v0.1490 SPTB Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: no specific treatment available (?Are these treatable by HSCT?)

Non-genetic confirmatory test: not assessed; to: Established gene-disease association.

Childhood onset, haematological disorder. Elliptocytosis, aneamia in some cases

Treatment: no specific treatment available (?Are these treatable by HSCT?)

Non-genetic confirmatory test: not assessed
BabyScreen+ newborn screening v0.1490 SPTB Seb Lunke Phenotypes for gene: SPTB were changed from Spherocytosis to Anaemia, neonatal haemolytic, fatal or near-fatal MIM# 617948
BabyScreen+ newborn screening v0.1488 SPTB Seb Lunke reviewed gene: SPTB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Anaemia, neonatal haemolytic, fatal or near-fatal MIM# 617948; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1488 SPTA1 Seb Lunke Marked gene: SPTA1 as ready
BabyScreen+ newborn screening v0.1485 PYGM Zornitza Stark Marked gene: PYGM as ready
BabyScreen+ newborn screening v0.1485 PYGM Zornitza Stark Phenotypes for gene: PYGM were changed from McCardle disease MIM# 608455 to McArdle disease, MIM# 232600; Glycogen storage disease, autosomal dominant
BabyScreen+ newborn screening v0.1482 PYGM Zornitza Stark reviewed gene: PYGM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: McArdle disease, MIM# 232600, Glycogen storage disease, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1482 RASA1 Zornitza Stark Marked gene: RASA1 as ready
BabyScreen+ newborn screening v0.1482 RASA1 Zornitza Stark Phenotypes for gene: RASA1 were changed from Capillary malformation-arteriovenous malformation to Capillary malformation-arteriovenous malformation 1, MIM#608354
BabyScreen+ newborn screening v0.1480 RASA1 Zornitza Stark reviewed gene: RASA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Capillary malformation-arteriovenous malformation 1, MIM#608354; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1480 RB1 Zornitza Stark Marked gene: RB1 as ready
BabyScreen+ newborn screening v0.1479 RAPSN Zornitza Stark Marked gene: RAPSN as ready
BabyScreen+ newborn screening v0.1478 RAG1 Zornitza Stark Marked gene: RAG1 as ready
BabyScreen+ newborn screening v0.1478 RAG1 Zornitza Stark Phenotypes for gene: RAG1 were changed from Omenn syndrome, MIM#603554 to Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457
BabyScreen+ newborn screening v0.1477 RAG1 Zornitza Stark reviewed gene: RAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889, Combined cellular and humoral immune defects with granulomas MIM# 233650, Omenn syndrome MIM# 603554, Severe combined immunodeficiency, B cell-negative MIM# 601457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1477 RAG2 Zornitza Stark Marked gene: RAG2 as ready
BabyScreen+ newborn screening v0.1477 RAG2 Zornitza Stark Phenotypes for gene: RAG2 were changed from Omenn syndrome, MIM#603554 to Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457; Combined cellular and humoral immune defects with granulomas MIM# 233650
BabyScreen+ newborn screening v0.1476 RAG2 Zornitza Stark reviewed gene: RAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Omenn syndrome MIM# 603554, Severe combined immunodeficiency, B cell-negative MIM# 601457, Combined cellular and humoral immune defects with granulomas MIM# 233650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1476 RAB7A Zornitza Stark Marked gene: RAB7A as ready
BabyScreen+ newborn screening v0.1476 RAB7A Zornitza Stark Phenotypes for gene: RAB7A were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 2B, MIM# 600882
BabyScreen+ newborn screening v0.1474 RAB7A Zornitza Stark reviewed gene: RAB7A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 2B, MIM# 600882; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1474 RAB3GAP2 Zornitza Stark Marked gene: RAB3GAP2 as ready
BabyScreen+ newborn screening v0.1473 RAB3GAP2 Zornitza Stark reviewed gene: RAB3GAP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Warburg micro syndrome 2, MIM# 614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1473 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
BabyScreen+ newborn screening v0.1473 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome to Warburg micro syndrome 1, MIM# 600118 Martsolf syndrome 2, MIM# 619420
BabyScreen+ newborn screening v0.1471 RAB3GAP1 Zornitza Stark reviewed gene: RAB3GAP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Warburg micro syndrome 1, MIM# 600118 Martsolf syndrome 2, MIM# 619420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1471 RAB27A Zornitza Stark Marked gene: RAB27A as ready
BabyScreen+ newborn screening v0.1470 ORAI1 Zornitza Stark Marked gene: ORAI1 as ready
BabyScreen+ newborn screening v0.1469 ORAI1 Zornitza Stark gene: ORAI1 was added
gene: ORAI1 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: ORAI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ORAI1 were set to Immunodeficiency 9, MIM# 612782
Review for gene: ORAI1 was set to GREEN
Added comment: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)

Included here for AR disease. Onset is in newborn period. Life-threatening.

Treatment: BMT.

Non-genetic confirmatory testing: T cell proliferation assay
Sources: Expert Review
BabyScreen+ newborn screening v0.1468 RAI1 Zornitza Stark Marked gene: RAI1 as ready
BabyScreen+ newborn screening v0.1466 RBM8A Zornitza Stark Marked gene: RBM8A as ready
BabyScreen+ newborn screening v0.1464 RAB23 Zornitza Stark Marked gene: RAB23 as ready
BabyScreen+ newborn screening v0.1464 RAB23 Zornitza Stark Phenotypes for gene: RAB23 were changed from Carpenter syndrome to Carpenter syndrome (MIM#201000)
BabyScreen+ newborn screening v0.1462 RAB23 Zornitza Stark reviewed gene: RAB23: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Carpenter syndrome (MIM#201000); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1462 RAF1 Zornitza Stark Marked gene: RAF1 as ready
BabyScreen+ newborn screening v0.1460 RDX Zornitza Stark Marked gene: RDX as ready
BabyScreen+ newborn screening v0.1460 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
BabyScreen+ newborn screening v0.1458 REN Zornitza Stark Marked gene: REN as ready
BabyScreen+ newborn screening v0.1458 REN Zornitza Stark Phenotypes for gene: REN were changed from Renal tubular dysgenesis to Renal tubular dysgenesis, MIM# 267430
BabyScreen+ newborn screening v0.1456 REN Zornitza Stark changed review comment from: Established gene-disease association.

Presents as fetal anuria leading to perinatal death.

No specific treatment.; to: Established gene-disease association.

Bi-allelic LOF variants cause renal tubular dysgenesis, which presents as fetal anuria leading to perinatal death.. Mono-allelic variants, likely through a different mechanism (mostly missense) cause tubulointerstitial disease. More severe phenotype associated with variants that are located in the protein leader peptide and affecting its co-translational insertion in the endoplasmic reticulum (ER).

No specific treatment for either.
BabyScreen+ newborn screening v0.1455 REN Zornitza Stark reviewed gene: REN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1455 RETREG1 Zornitza Stark Marked gene: RETREG1 as ready
BabyScreen+ newborn screening v0.1455 RETREG1 Zornitza Stark Phenotypes for gene: RETREG1 were changed from MONDO:0013142; Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115 to Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115
BabyScreen+ newborn screening v0.1453 RETREG1 Zornitza Stark reviewed gene: RETREG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1453 RFWD3 Zornitza Stark Marked gene: RFWD3 as ready
BabyScreen+ newborn screening v0.1452 CIITA Zornitza Stark Marked gene: CIITA as ready
BabyScreen+ newborn screening v0.1451 CIITA Zornitza Stark gene: CIITA was added
gene: CIITA was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CIITA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CIITA were set to Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920
Review for gene: CIITA was set to GREEN
Added comment: 13 individuals of 11 unrelated families; two mouse models. Homozygous and compound heterozygous variants were identified in these individuals (missense, nonsense and splicing) resulting in premature stop codon and truncated protein, or inactive protein. Affected individuals typically present in infancy with severe (recurrent) respiratory and gastrointestinal tract infections and defective MHC II expression in PBMCs

Treatment: BMT.
Sources: Expert Review
BabyScreen+ newborn screening v0.1450 RFXAP Zornitza Stark Marked gene: RFXAP as ready
BabyScreen+ newborn screening v0.1449 RFXAP Zornitza Stark gene: RFXAP was added
gene: RFXAP was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: RFXAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RFXAP were set to Bare lymphocyte syndrome, type II, complementation group D MIM# 209920
Review for gene: RFXAP was set to GREEN
Added comment: 9 unique RFXAP variants in 12 unrelated individuals have been reported; one mouse model

The most frequent variant is a deletion c. delG484fsX525 which has been identified in 4 individuals of different origins (North African, Turkish and East Asian).

Typically presents in infancy with recurrent bacterial infections, severe diarrhoea and failure to thrive.

Treatment: BMT.
Sources: Expert Review
BabyScreen+ newborn screening v0.1448 RFX5 Zornitza Stark Marked gene: RFX5 as ready
BabyScreen+ newborn screening v0.1447 RFX5 Zornitza Stark gene: RFX5 was added
gene: RFX5 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: RFX5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RFX5 were set to Bare lymphocyte syndrome, type II, complementation group C MIM# 209920; Bare lymphocyte syndrome, type II, complementation group E MIM# 209920
Review for gene: RFX5 was set to GREEN
Added comment: Bare lymphocyte syndrome, type II, complementation group C

9 individuals from 8 unrelated families; multiple mouse models
Homozygous and Compound heterozygous (Nonsense, missense, splice site, single bp del) variants were reported resulting in truncated protein and loss of function.
All individuals presented with recurrent lower respiratory tract infection early in life, low CD4+ cells and/or failure to thrive, chronic diarrhoea, hepatosplenomegaly and low Ig levels.
----------
Bare lymphocyte syndrome, type II, complementation group E

2 siblings (twins) reported with RPX5 variants and new BLS group E phenotype; multiple functional studies
Identified homozygous missense variant (R149Q) which resulted in altered DNA-binding domain and loss of function.
These histo-identical twin brothers had normal numbers of CD4 + cells and are able to mount both cellular and humoral immune responses. They displayed absence of MHC class II surface expression on B cells and mononuclear cells.

Presentation is typically in infancy.

Treatment: BMT.
Sources: Expert Review
BabyScreen+ newborn screening v0.1446 RFXANK Zornitza Stark Marked gene: RFXANK as ready
BabyScreen+ newborn screening v0.1446 RMRP Zornitza Stark Marked gene: RMRP as ready
BabyScreen+ newborn screening v0.1446 RMRP Zornitza Stark Phenotypes for gene: RMRP were changed from Cartilage-hair hypoplasia to Cartilage-hair hypoplasia MIM#250250
BabyScreen+ newborn screening v0.1445 RMRP Zornitza Stark reviewed gene: RMRP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cartilage-hair hypoplasia MIM#250250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1445 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
BabyScreen+ newborn screening v0.1445 RNASEH2A Zornitza Stark Phenotypes for gene: RNASEH2A were changed from Aicardi-Goutieres syndrome to Aicardi-Goutieres syndrome 4, MIM# 610333
BabyScreen+ newborn screening v0.1443 RNASEH2A Zornitza Stark reviewed gene: RNASEH2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 4, MIM# 610333; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1443 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
BabyScreen+ newborn screening v0.1443 RNASEH2B Zornitza Stark Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome to Aicardi-Goutieres syndrome 2, MIM# 610181
BabyScreen+ newborn screening v0.1440 RNASEH2B Zornitza Stark reviewed gene: RNASEH2B: Rating: AMBER; Mode of pathogenicity: None; Publications: 32877590; Phenotypes: Aicardi-Goutieres syndrome 2, MIM# 610181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1440 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
BabyScreen+ newborn screening v0.1440 RNASEH2C Zornitza Stark Phenotypes for gene: RNASEH2C were changed from Aicardi-Goutieres syndrome to Aicardi-Goutieres syndrome 3, MIM# 610329
BabyScreen+ newborn screening v0.1437 RNASEH2C Zornitza Stark reviewed gene: RNASEH2C: Rating: AMBER; Mode of pathogenicity: None; Publications: 32877590; Phenotypes: Aicardi-Goutieres syndrome 3, MIM# 610329; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1437 ROR2 Zornitza Stark Marked gene: ROR2 as ready
BabyScreen+ newborn screening v0.1434 RPGR Zornitza Stark Marked gene: RPGR as ready
BabyScreen+ newborn screening v0.1432 RPGRIP1L Zornitza Stark Marked gene: RPGRIP1L as ready
BabyScreen+ newborn screening v0.1430 RPL11 Zornitza Stark Marked gene: RPL11 as ready
BabyScreen+ newborn screening v0.1430 RPL15 Zornitza Stark Marked gene: RPL15 as ready
BabyScreen+ newborn screening v0.1430 RPL18 Zornitza Stark Marked gene: RPL18 as ready
BabyScreen+ newborn screening v0.1429 RPL26 Zornitza Stark Marked gene: RPL26 as ready
BabyScreen+ newborn screening v0.1428 RPL27 Zornitza Stark Marked gene: RPL27 as ready
BabyScreen+ newborn screening v0.1427 RPL35 Zornitza Stark Marked gene: RPL35 as ready
BabyScreen+ newborn screening v0.1426 RPL5 Zornitza Stark Marked gene: RPL5 as ready
BabyScreen+ newborn screening v0.1426 KARS Zornitza Stark Classified gene: KARS as Red List (low evidence)
BabyScreen+ newborn screening v0.1426 KARS Zornitza Stark Gene: kars has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1425 KARS Zornitza Stark Tag for review was removed from gene: KARS.
BabyScreen+ newborn screening v0.1425 KARS Zornitza Stark changed review comment from: Variants in this gene are associated with either isolated or complex deafness with leukoencephalopathy.

The deafness tends to be congenital/pre-lingual. For review, likely meets criteria though some individuals will have leukoencephalopathy which does not have a specific treatment.; to: Variants in this gene are associated with either isolated or complex deafness with leukoencephalopathy.

The deafness tends to be congenital/pre-lingual. For review, likely meets criteria though some individuals will have leukoencephalopathy which does not have a specific treatment.

Reviewed: significant uncertainty regarding outcome, exclude.
BabyScreen+ newborn screening v0.1425 KARS Zornitza Stark edited their review of gene: KARS: Changed rating: RED
BabyScreen+ newborn screening v0.1425 RYR1 Zornitza Stark changed review comment from: Well established association with susceptibility to malignant hyperthermia.

However, variants in this gene also cause a range of muscular phenotypes, for which there is no specific treatment.

Association with malignant hyperthermia is rated 'strongly actionable' in children by ClinGen.

MH susceptibility (MHS) is a pharmacogenetic skeletal muscle disorder where exposure to certain volatile anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, sevoflurane), either alone or with a depolarizing muscle relaxant (succinylcholine), may trigger uncontrolled skeletal muscle hypermetabolism. An MH episode may begin with hypercapnia, rapidly rising end-tidal CO2, and tachycardia followed by hyperthermia. Additional symptoms may include acidosis, muscle rigidity, compartment syndrome, rhabdomyolysis and subsequent increased creatine kinase, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure.

There is mounting evidence that some individuals with MHS may also develop episodes triggered by non-anesthetic conditions such as heat and/or exercise. These non-anesthetic-induced episodes, often called MH-like syndrome, may manifest as exertional rhabdomyolysis (ER).

Surgical management recommendations include preparation of the anesthesia workstation to reduce or prevent exposure to triggering anesthetics (e.g., remove vaporizers from machine and replace all disposables), vigilant monitoring for signs and symptoms of MH during perioperative period, and close observation and monitoring postoperatively.

MHS patients should carry identification of their susceptibility and inform those responsible for their care of their MH status.

Do not use the following MH triggering drugs for MHS patients: inhaled general anesthetics (desflurane, enflurane, halothane, isoflurane, sevoflurane) and depolarizing muscle relaxants (succinylcholine).

For review.; to: Well established association with susceptibility to malignant hyperthermia.

However, variants in this gene also cause a range of muscular phenotypes, for which there is no specific treatment.

Association with malignant hyperthermia is rated 'strongly actionable' in children by ClinGen.

MH susceptibility (MHS) is a pharmacogenetic skeletal muscle disorder where exposure to certain volatile anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, sevoflurane), either alone or with a depolarizing muscle relaxant (succinylcholine), may trigger uncontrolled skeletal muscle hypermetabolism. An MH episode may begin with hypercapnia, rapidly rising end-tidal CO2, and tachycardia followed by hyperthermia. Additional symptoms may include acidosis, muscle rigidity, compartment syndrome, rhabdomyolysis and subsequent increased creatine kinase, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure.

There is mounting evidence that some individuals with MHS may also develop episodes triggered by non-anesthetic conditions such as heat and/or exercise. These non-anesthetic-induced episodes, often called MH-like syndrome, may manifest as exertional rhabdomyolysis (ER).

Surgical management recommendations include preparation of the anesthesia workstation to reduce or prevent exposure to triggering anesthetics (e.g., remove vaporizers from machine and replace all disposables), vigilant monitoring for signs and symptoms of MH during perioperative period, and close observation and monitoring postoperatively.

MHS patients should carry identification of their susceptibility and inform those responsible for their care of their MH status.

Do not use the following MH triggering drugs for MHS patients: inhaled general anesthetics (desflurane, enflurane, halothane, isoflurane, sevoflurane) and depolarizing muscle relaxants (succinylcholine).
BabyScreen+ newborn screening v0.1425 DMD Zornitza Stark changed review comment from: Well established gene-disease association. Milder phenotypes such as BMD and DCM are also associated with variants in this gene. Females typically at risk for cardiac disease only.

Onset in early childhood.

Treatment: Eteplirsen, Casimersen and Golodirsen for exon skipping 51, 45 and 53, respectively. Vitolarsen has also been approved for exon 53 skipping.

Pilots are underway to assess NBS for DMD, including one planned in NSW. Most programs are based on raised CK levels.

For review.; to: Well established gene-disease association. Milder phenotypes such as BMD and DCM are also associated with variants in this gene. Females typically at risk for cardiac disease only.

Onset in early childhood.

Treatment: Eteplirsen, Casimersen and Golodirsen for exon skipping 51, 45 and 53, respectively. Vitolarsen has also been approved for exon 53 skipping.

Pilots are underway to assess NBS for DMD, including one planned in NSW. Most programs are based on raised CK levels.

For review. Discuss with neurology. Should we only report variants that are likely to benefit from treatment?
BabyScreen+ newborn screening v0.1425 SPRED1 Seb Lunke Marked gene: SPRED1 as ready
BabyScreen+ newborn screening v0.1423 DMD Zornitza Stark Marked gene: DMD as ready
BabyScreen+ newborn screening v0.1423 DMD Zornitza Stark Phenotypes for gene: DMD were changed from Becker muscular dystrophy; Duchenne muscular dystrophy, MIM# 310200; Duchenne muscular dystrophy; Cardiomyopathy, dilated to Duchenne muscular dystrophy MIM#310200
BabyScreen+ newborn screening v0.1420 DMD Zornitza Stark reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 36278620, 36152336, 35562557, 35307847; Phenotypes: Duchenne muscular dystrophy MIM#310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1420 SPR Seb Lunke Marked gene: SPR as ready
BabyScreen+ newborn screening v0.1418 SPINK5 Seb Lunke Marked gene: SPINK5 as ready
BabyScreen+ newborn screening v0.1416 SPEG Seb Lunke Marked gene: SPEG as ready
BabyScreen+ newborn screening v0.1415 SPEG Seb Lunke reviewed gene: SPEG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Centronuclear myopathy 5, MIM# 615959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1415 SP110 Seb Lunke Marked gene: SP110 as ready
BabyScreen+ newborn screening v0.1414 SOX9 Seb Lunke Marked gene: SOX9 as ready
BabyScreen+ newborn screening v0.1412 SOX10 Seb Lunke Marked gene: SOX10 as ready
BabyScreen+ newborn screening v0.1411 SNAP25 Seb Lunke Marked gene: SNAP25 as ready
BabyScreen+ newborn screening v0.1408 SMPX Seb Lunke Marked gene: SMPX as ready
BabyScreen+ newborn screening v0.1408 SMPX Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, neuro-muscular disorder

Treatment: no specific treatment available

Non-genetic confirmatory test: not assessed; to: Established gene-disease association.

Childhood onset, deafness

Treatment: no specific treatment available

Non-genetic confirmatory test: not assessed
BabyScreen+ newborn screening v0.1406 SMPD1 Seb Lunke Marked gene: SMPD1 as ready
BabyScreen+ newborn screening v0.1404 SMC1A Seb Lunke Marked gene: SMC1A as ready
BabyScreen+ newborn screening v0.1404 SMC1A Seb Lunke Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome 2, MIM# 300590; Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044
BabyScreen+ newborn screening v0.1401 SMC1A Seb Lunke reviewed gene: SMC1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 2, MIM# 300590, Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1401 SMAD3 Zornitza Stark Tag cardiac tag was added to gene: SMAD3.
BabyScreen+ newborn screening v0.1401 SMARCAL1 Zornitza Stark Tag immunological tag was added to gene: SMARCAL1.
BabyScreen+ newborn screening v0.1400 RPS15 Zornitza Stark Marked gene: RPS15 as ready
BabyScreen+ newborn screening v0.1397 RPS15A Zornitza Stark Marked gene: RPS15A as ready
BabyScreen+ newborn screening v0.1396 RPS17 Zornitza Stark Marked gene: RPS17 as ready
BabyScreen+ newborn screening v0.1396 RPS19 Zornitza Stark Marked gene: RPS19 as ready
BabyScreen+ newborn screening v0.1396 RPS24 Zornitza Stark Marked gene: RPS24 as ready
BabyScreen+ newborn screening v0.1396 RPS26 Zornitza Stark Marked gene: RPS26 as ready
BabyScreen+ newborn screening v0.1396 SMARCAL1 Seb Lunke Marked gene: SMARCAL1 as ready
BabyScreen+ newborn screening v0.1396 SMARCAL1 Seb Lunke Gene: smarcal1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1396 SMARCAL1 Seb Lunke Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia to Schimke immune-osseous dysplasia MIM# 242900
BabyScreen+ newborn screening v0.1395 SMARCAL1 Seb Lunke Classified gene: SMARCAL1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1395 SMARCAL1 Seb Lunke Gene: smarcal1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1394 SMARCAL1 Seb Lunke Tag for review tag was added to gene: SMARCAL1.
BabyScreen+ newborn screening v0.1394 SMARCAL1 Seb Lunke reviewed gene: SMARCAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Schimke immune-osseous dysplasia MIM# 242900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1394 SMAD4 Seb Lunke Marked gene: SMAD4 as ready
BabyScreen+ newborn screening v0.1391 SMAD3 Seb Lunke Marked gene: SMAD3 as ready
BabyScreen+ newborn screening v0.1389 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
BabyScreen+ newborn screening v0.1386 RPS27 Zornitza Stark Marked gene: RPS27 as ready
BabyScreen+ newborn screening v0.1385 RPS28 Zornitza Stark Marked gene: RPS28 as ready
BabyScreen+ newborn screening v0.1384 RPS29 Zornitza Stark Marked gene: RPS29 as ready
BabyScreen+ newborn screening v0.1383 RPS6KA3 Zornitza Stark Marked gene: RPS6KA3 as ready
BabyScreen+ newborn screening v0.1381 RRM2B Zornitza Stark Marked gene: RRM2B as ready
BabyScreen+ newborn screening v0.1379 RS1 Zornitza Stark Marked gene: RS1 as ready
BabyScreen+ newborn screening v0.1377 RSPH4A Zornitza Stark Marked gene: RSPH4A as ready
BabyScreen+ newborn screening v0.1377 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from Ciliary dyskinesia, primary to Ciliary dyskinesia, primary, 11 (MIM#612649)
BabyScreen+ newborn screening v0.1375 RSPH4A Zornitza Stark reviewed gene: RSPH4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 11 (MIM#612649); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1375 RSPH9 Zornitza Stark Marked gene: RSPH9 as ready
BabyScreen+ newborn screening v0.1375 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from Ciliary dyskinesia, primary to Ciliary dyskinesia, primary, 12 (MIM#612650)
BabyScreen+ newborn screening v0.1373 RSPH9 Zornitza Stark reviewed gene: RSPH9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 12 (MIM#612650); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1373 RUNX2 Zornitza Stark Marked gene: RUNX2 as ready
BabyScreen+ newborn screening v0.1373 RUNX2 Zornitza Stark Phenotypes for gene: RUNX2 were changed from Cleidocranial dysostosis to Cleidocranial dysplasia MIM#119600; Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600; Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510
BabyScreen+ newborn screening v0.1371 RUNX2 Zornitza Stark reviewed gene: RUNX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleidocranial dysplasia MIM#119600, Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600, Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600, Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1371 CACNA1S Zornitza Stark Marked gene: CACNA1S as ready
BabyScreen+ newborn screening v0.1369 CACNA1S Zornitza Stark Tag for review tag was added to gene: CACNA1S.
Tag pharmacogenomic tag was added to gene: CACNA1S.
BabyScreen+ newborn screening v0.1369 RYR1 Zornitza Stark Marked gene: RYR1 as ready
BabyScreen+ newborn screening v0.1367 RYR1 Zornitza Stark Tag for review tag was added to gene: RYR1.
Tag pharmacogenomic tag was added to gene: RYR1.
BabyScreen+ newborn screening v0.1367 RYR2 Zornitza Stark Marked gene: RYR2 as ready
BabyScreen+ newborn screening v0.1367 RYR2 Zornitza Stark Tag for review tag was added to gene: RYR2.
Tag cardiac tag was added to gene: RYR2.
Tag treatable tag was added to gene: RYR2.
BabyScreen+ newborn screening v0.1367 RYR2 Zornitza Stark reviewed gene: RYR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 1, MIM# 604772; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1367 INSR Zornitza Stark Marked gene: INSR as ready
BabyScreen+ newborn screening v0.1364 SLX4 Seb Lunke Marked gene: SLX4 as ready
BabyScreen+ newborn screening v0.1364 SLCO2A1 Seb Lunke Marked gene: SLCO2A1 as ready
BabyScreen+ newborn screening v0.1363 SLCO2A1 Seb Lunke reviewed gene: SLCO2A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1363 SLC9A6 Seb Lunke Marked gene: SLC9A6 as ready
BabyScreen+ newborn screening v0.1363 SLC9A6 Seb Lunke Phenotypes for gene: SLC9A6 were changed from Christianson syndrome to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243
BabyScreen+ newborn screening v0.1361 SLC9A6 Seb Lunke reviewed gene: SLC9A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1361 SLC7A9 Seb Lunke Marked gene: SLC7A9 as ready
BabyScreen+ newborn screening v0.1361 SLC7A9 Seb Lunke Added comment: Comment when marking as ready: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: no specific treatment available

Non-genetic confirmatory test: not assessed
BabyScreen+ newborn screening v0.1359 SLC7A7 Seb Lunke edited their review of gene: SLC7A7: Added comment: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: protein restriction, carnitine, citrulline, lysine supplementation, sodium benzoate

Non-genetic confirmatory test: 24-hour urinary excretion of cationic amino acids; Changed publications: 20301535
BabyScreen+ newborn screening v0.1359 SLC7A7 Seb Lunke Marked gene: SLC7A7 as ready
BabyScreen+ newborn screening v0.1355 SLC6A5 Seb Lunke Marked gene: SLC6A5 as ready
BabyScreen+ newborn screening v0.1354 SLC6A19 Seb Lunke Marked gene: SLC6A19 as ready
BabyScreen+ newborn screening v0.1353 SLC6A19 Seb Lunke reviewed gene: SLC6A19: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hartnup disorder, MIM# 234500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1353 SLC5A5 Seb Lunke Marked gene: SLC5A5 as ready
BabyScreen+ newborn screening v0.1351 SLC5A1 Seb Lunke Marked gene: SLC5A1 as ready
BabyScreen+ newborn screening v0.1351 SLC52A3 Seb Lunke Marked gene: SLC52A3 as ready
BabyScreen+ newborn screening v0.1350 SLC52A2 Seb Lunke Marked gene: SLC52A2 as ready
BabyScreen+ newborn screening v0.1350 SLC4A11 Seb Lunke Marked gene: SLC4A11 as ready
BabyScreen+ newborn screening v0.1347 INS Zornitza Stark Marked gene: INS as ready
BabyScreen+ newborn screening v0.1347 INS Zornitza Stark Phenotypes for gene: INS were changed from Diabetes mellitus, permanent neonatal MIM# 618858Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life to Diabetes mellitus, insulin-dependent, 2, MIM# 125852; Diabetes mellitus, permanent neonatal 4, MIM# 618858; Maturity-onset diabetes of the young, type 10, MIM# 613370
BabyScreen+ newborn screening v0.1345 HBB Zornitza Stark Marked gene: HBB as ready
BabyScreen+ newborn screening v0.1344 HBA2 Zornitza Stark Marked gene: HBA2 as ready
BabyScreen+ newborn screening v0.1344 HBA1 Zornitza Stark Marked gene: HBA1 as ready
BabyScreen+ newborn screening v0.1344 SLC4A1 Seb Lunke Marked gene: SLC4A1 as ready
BabyScreen+ newborn screening v0.1344 SLC4A1 Seb Lunke Phenotypes for gene: SLC4A1 were changed from Spherocytosis to Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590
BabyScreen+ newborn screening v0.1341 SLC4A1 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, metabolic condition

Treatment: oral alkali replacement therapy, potassium chloride

Non-genetic confirmatory test: serum bicarbonate, chloride, potassium, urinary pH and anion gap; to: Established gene-disease association.

Childhood onset, metabolic condition

Treatment: oral alkali replacement therapy, potassium chloride. Not clear if treatment equally applicable to dominant and recessive forms of disease

Non-genetic confirmatory test: serum bicarbonate, chloride, potassium, urinary pH and anion gap
BabyScreen+ newborn screening v0.1341 SLC4A1 Seb Lunke reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31600044; Phenotypes: Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1341 SLC46A1 Seb Lunke Marked gene: SLC46A1 as ready
BabyScreen+ newborn screening v0.1341 SLC46A1 Seb Lunke Phenotypes for gene: SLC46A1 were changed from Folate malabsorption, hereditary, MIM# to Folate malabsorption, hereditary, MIM# 229050
BabyScreen+ newborn screening v0.1340 SLC46A1 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, metabolic disorders

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels; to: Established gene-disease association.

Childhood onset, metabolic disorder

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels
BabyScreen+ newborn screening v0.1340 SLC46A1 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset,

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels; to: Established gene-disease association.

Childhood onset, metabolic disorders

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels
BabyScreen+ newborn screening v0.1340 SLC46A1 Seb Lunke reviewed gene: SLC46A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301716; Phenotypes: Folate malabsorption, hereditary, MIM# 229050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1340 SLC45A2 Seb Lunke Marked gene: SLC45A2 as ready
BabyScreen+ newborn screening v0.1338 SLC3A1 Seb Lunke Marked gene: SLC3A1 as ready
BabyScreen+ newborn screening v0.1336 SLC39A8 Seb Lunke Marked gene: SLC39A8 as ready
BabyScreen+ newborn screening v0.1335 SLC39A4 Seb Lunke Marked gene: SLC39A4 as ready
BabyScreen+ newborn screening v0.1333 SLC37A4 Seb Lunke Marked gene: SLC37A4 as ready
BabyScreen+ newborn screening v0.1331 SLC37A4 Seb Lunke edited their review of gene: SLC37A4: Added comment: Established gene-disease association.

Childhood onset, metabolic disorder

Treatment: corn starch, nighttime intragastric continuous glucose infusion, allopurinol, statin, granulocyte-colony stimulating factor (G-CSF), empagliflozin

Non-genetic confirmatory test: no; Changed phenotypes: Glycogen storage disease Ib, MIM# 232220, Glycogen storage disease Ic, MIM# 232240, Congenital disorder of glycosylation, type IIw, MIM# 619525
BabyScreen+ newborn screening v0.1331 SLC35D1 Seb Lunke Marked gene: SLC35D1 as ready
BabyScreen+ newborn screening v0.1329 SLC34A2 Seb Lunke Marked gene: SLC34A2 as ready
BabyScreen+ newborn screening v0.1329 SLC34A2 Seb Lunke Phenotypes for gene: SLC34A2 were changed from Pulmonary alveolar microlithiasis to Pulmonary alveolar microlithiasis, MIM# 265100
BabyScreen+ newborn screening v0.1327 SLC34A2 Seb Lunke reviewed gene: SLC34A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary alveolar microlithiasis, MIM# 265100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1327 SLC2A10 Seb Lunke Marked gene: SLC2A10 as ready
BabyScreen+ newborn screening v0.1327 SLC2A10 Seb Lunke Phenotypes for gene: SLC2A10 were changed from Arterial tortuosity syndrome to Arterial tortuosity syndrome MIM#208050
BabyScreen+ newborn screening v0.1325 SLC2A10 Seb Lunke reviewed gene: SLC2A10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial tortuosity syndrome MIM#208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1325 SLC2A1 Seb Lunke Marked gene: SLC2A1 as ready
BabyScreen+ newborn screening v0.1323 SLC27A4 Seb Lunke Marked gene: SLC27A4 as ready
BabyScreen+ newborn screening v0.1320 SLC26A4 Seb Lunke Marked gene: SLC26A4 as ready
BabyScreen+ newborn screening v0.1317 SLC39A7 Seb Lunke Marked gene: SLC39A7 as ready
BabyScreen+ newborn screening v0.1316 SLC39A7 Seb Lunke gene: SLC39A7 was added
gene: SLC39A7 was added to gNBS. Sources: Literature
Mode of inheritance for gene: SLC39A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A7 were set to 30718914
Phenotypes for gene: SLC39A7 were set to Agammaglobulinaemia 9, autosomal recessive, MIM# 619693
Added comment: Established gene-disease association.

Childhood onset, primary immunodeficiency

Treatment: Bone marrow transplant (hematopoietic stem cell transplantation (HSCT)), replacement immunoglobulin treatment

Non-genetic confirmatory test: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile
Sources: Literature
BabyScreen+ newborn screening v0.1315 SLC35C1 Seb Lunke Marked gene: SLC35C1 as ready
BabyScreen+ newborn screening v0.1312 SLC35A2 Seb Lunke Marked gene: SLC35A2 as ready
BabyScreen+ newborn screening v0.1312 SLC35A2 Seb Lunke Phenotypes for gene: SLC35A2 were changed from Early-onset epileptic encephalopathy to Congenital disorder of glycosylation, type IIm, MIM #300896
BabyScreen+ newborn screening v0.1309 SLC30A10 Seb Lunke Marked gene: SLC30A10 as ready
BabyScreen+ newborn screening v0.1307 SLC39A14 Seb Lunke Marked gene: SLC39A14 as ready
BabyScreen+ newborn screening v0.1306 SLC39A14 Seb Lunke gene: SLC39A14 was added
gene: SLC39A14 was added to gNBS. Sources: Literature
Mode of inheritance for gene: SLC39A14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A14 were set to 31089831
Phenotypes for gene: SLC39A14 were set to Hypermanganesemia with dystonia 2, MIM# 617013
Review for gene: SLC39A14 was set to AMBER
Added comment: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: manganese chelation therapy with EDTA-CaNa2 with strong improvements in one patient, less effective in multiple others. Age of treatment start (earlier = better) and genotype may impact outcome.

Non-genetic confirmatory test: Mn level
Sources: Literature
BabyScreen+ newborn screening v0.1305 GLA Zornitza Stark Marked gene: GLA as ready
BabyScreen+ newborn screening v0.1303 GGCX Zornitza Stark Marked gene: GGCX as ready
BabyScreen+ newborn screening v0.1302 GNPTG Zornitza Stark Marked gene: GNPTG as ready
BabyScreen+ newborn screening v0.1299 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
BabyScreen+ newborn screening v0.1298 HCFC1 Zornitza Stark Marked gene: HCFC1 as ready
BabyScreen+ newborn screening v0.1295 HNF1A Zornitza Stark Marked gene: HNF1A as ready
BabyScreen+ newborn screening v0.1294 HNF4A Zornitza Stark Marked gene: HNF4A as ready
BabyScreen+ newborn screening v0.1294 HNF4A Zornitza Stark Phenotypes for gene: HNF4A were changed from Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, MIM# 616026; Hypoglycaemia, hyperinsulinaemic, MIM#125850 to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, MIM# 616026; Hypoglycaemia, hyperinsulinaemic, MIM#125850; MODY, type I, OMIM # 125850
BabyScreen+ newborn screening v0.1292 HNF4A Zornitza Stark reviewed gene: HNF4A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM #616026, MODY, type I, OMIM # 125850; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1292 HOMER2 Zornitza Stark Marked gene: HOMER2 as ready
BabyScreen+ newborn screening v0.1290 HPS1 Zornitza Stark Marked gene: HPS1 as ready
BabyScreen+ newborn screening v0.1288 HPS3 Zornitza Stark Marked gene: HPS3 as ready
BabyScreen+ newborn screening v0.1286 HPS4 Zornitza Stark Marked gene: HPS4 as ready
BabyScreen+ newborn screening v0.1284 HPS5 Zornitza Stark Marked gene: HPS5 as ready
BabyScreen+ newborn screening v0.1282 PIGA Zornitza Stark Marked gene: PIGA as ready
BabyScreen+ newborn screening v0.1281 HSD17B10 Zornitza Stark Marked gene: HSD17B10 as ready
BabyScreen+ newborn screening v0.1278 HPRT1 Zornitza Stark Marked gene: HPRT1 as ready
BabyScreen+ newborn screening v0.1275 HPRT1 Zornitza Stark changed review comment from: Uncertain if these are symptomatic treatments.; to: Uncertain if these are essentially symptomatic treatments.
BabyScreen+ newborn screening v0.1275 HPRT1 Zornitza Stark commented on gene: HPRT1: Uncertain if these are symptomatic treatments.
BabyScreen+ newborn screening v0.1275 HGD Zornitza Stark Marked gene: HGD as ready
BabyScreen+ newborn screening v0.1272 KARS John Christodoulou reviewed gene: KARS: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29615062; Phenotypes: leukoencephalopathy, SNHL, neurodenegeration, cardiomyopathy, visual loss; Mode of inheritance: None
BabyScreen+ newborn screening v0.1272 IDUA John Christodoulou reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30143438; Phenotypes: coarse facie, corneal clouding, progressive neurodegeneration, dysostosis multiplex, hepatosplenomegaly, hernias, macrocephaly, cardiac valve involvement, SNHL, upper airways obstruction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1272 IDS John Christodoulou reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30143438, PMID: 33004112; Phenotypes: coarse facial features, cardiac valve involvement, hepatosplenomegaly, cardiomyopathy, airway obstruction, hydrocephalus, SNHL, dysostosis multiplex, kyphoscoliosis, progressive cognitive decline; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1272 HSD17B10 John Christodoulou reviewed gene: HSD17B10: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22127393; Phenotypes: cardiomyopathy, early-onset intractable seizures, progressive choreoathetosis, spastic tetraplegia, optic atrophy, retinal degeneration, intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1272 HGD John Christodoulou reviewed gene: HGD: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34344451, PMID: 12501223, PMID: 12501223; Phenotypes: progressive arthritis, progressive calcific cardiac valve damage, renal stones; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1272 HSD17B3 Zornitza Stark Marked gene: HSD17B3 as ready
BabyScreen+ newborn screening v0.1270 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
BabyScreen+ newborn screening v0.1270 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from D-bifunctional protein deficiency to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
BabyScreen+ newborn screening v0.1268 HSD17B4 Zornitza Stark changed review comment from: Well established association with peroxisomal disorders.

Congenital onset, variable severity.

No specific treatment.; to: Well established association with peroxisomal disorders.

Congenital onset, variable severity. SNHL is of childhood onset.

No specific treatment.
BabyScreen+ newborn screening v0.1268 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1268 HSD3B2 Zornitza Stark Marked gene: HSD3B2 as ready
BabyScreen+ newborn screening v0.1268 HSD3B7 Zornitza Stark Marked gene: HSD3B7 as ready
BabyScreen+ newborn screening v0.1267 HSPB8 Zornitza Stark Marked gene: HSPB8 as ready
BabyScreen+ newborn screening v0.1267 HSPB8 Zornitza Stark Phenotypes for gene: HSPB8 were changed from Charcot-Marie-Tooth disease, axonal, type 2L to Neuropathy, distal hereditary motor type IIA, 158590; Charcot-Marie-Tooth disease, axonal, type 2L, MIM# 608673
BabyScreen+ newborn screening v0.1265 HSPB8 Zornitza Stark reviewed gene: HSPB8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, distal hereditary motor type IIA, 158590, Charcot-Marie-Tooth disease, axonal, type 2L, MIM# 608673; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1265 HSPG2 Zornitza Stark Marked gene: HSPG2 as ready
BabyScreen+ newborn screening v0.1265 HSPG2 Zornitza Stark Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome to Schwartz-Jampel syndrome, type 1, MIM# 255800; MONDO:0009717; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; MONDO:0009140
BabyScreen+ newborn screening v0.1263 HSPG2 Zornitza Stark reviewed gene: HSPG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM# 255800, MONDO:0009717, Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410, MONDO:0009140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1263 HTRA1 Zornitza Stark Marked gene: HTRA1 as ready
BabyScreen+ newborn screening v0.1263 HTRA1 Zornitza Stark Phenotypes for gene: HTRA1 were changed from CARASIL syndrome to CARASIL syndrome, MIM# 600142
BabyScreen+ newborn screening v0.1261 HTRA1 Zornitza Stark reviewed gene: HTRA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: CARASIL syndrome, MIM# 600142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1261 SLC4A4 Seb Lunke Marked gene: SLC4A4 as ready
BabyScreen+ newborn screening v0.1261 SLC4A4 Seb Lunke Phenotypes for gene: SLC4A4 were changed from Renal tubular acidosis, proximal, with ocular abnormalities to Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278
BabyScreen+ newborn screening v0.1260 SLC4A4 Seb Lunke reviewed gene: SLC4A4: Rating: RED; Mode of pathogenicity: None; Publications: 24978391; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1260 ILDR1 Zornitza Stark Marked gene: ILDR1 as ready
BabyScreen+ newborn screening v0.1259 IL2RB Zornitza Stark Marked gene: IL2RB as ready
BabyScreen+ newborn screening v0.1259 SLC5A6 Seb Lunke Marked gene: SLC5A6 as ready
BabyScreen+ newborn screening v0.1257 SLC5A6 Seb Lunke gene: SLC5A6 was added
gene: SLC5A6 was added to gNBS. Sources: Literature
for review tags were added to gene: SLC5A6.
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: SLC5A6 was set to GREEN
Added comment: Established gene-disease association.

Childhood onset, multisystemic metabolic disorder with highly variable manifestations

Treatment: biotin, pantothenic acid, lipoate

Non-genetic confirmatory test: no
Sources: Literature
BabyScreen+ newborn screening v0.1256 SLC5A7 Seb Lunke Marked gene: SLC5A7 as ready
BabyScreen+ newborn screening v0.1255 SLC5A7 Seb Lunke gene: SLC5A7 was added
gene: SLC5A7 was added to gNBS. Sources: Literature
Mode of inheritance for gene: SLC5A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A7 were set to 20301347
Phenotypes for gene: SLC5A7 were set to Myasthenic syndrome, congenital, 20, presynaptic, MIM# 617143
Review for gene: SLC5A7 was set to GREEN
Added comment: Established gene-disease association.

Childhood onset, severe neuromuscular disorder
(recessive disease)

Treatment: Salbutamol, Acetylcholine-esterase inhibitors

Non-genetic confirmatory test: repetitive nerve stimulation test
Sources: Literature
BabyScreen+ newborn screening v0.1254 SLC9A3 Seb Lunke Marked gene: SLC9A3 as ready
BabyScreen+ newborn screening v0.1253 SLC9A3 Seb Lunke gene: SLC9A3 was added
gene: SLC9A3 was added to gNBS. Sources: Literature
for review tags were added to gene: SLC9A3.
Mode of inheritance for gene: SLC9A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC9A3 were set to Diarrhoea 8, secretory sodium, congenital, MiM# 616868
Review for gene: SLC9A3 was set to AMBER
Added comment: Established gene-disease association.

Childhood onset, congenital diarrhea. ?severity

Treatment: sodium, bicarbonate

Non-genetic confirmatory test: fecal sodium concentration
Sources: Literature
BabyScreen+ newborn screening v0.1251 ADA2 Seb Lunke Marked gene: ADA2 as ready
BabyScreen+ newborn screening v0.1251 ADA2 Seb Lunke gene: ADA2 was added
gene: ADA2 was added to gNBS. Sources: Literature
for review tags were added to gene: ADA2.
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADA2 were set to Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688
Review for gene: ADA2 was set to GREEN
Added comment: Established gene-disease association.

Childhood onset but variable, multisystem disorder with variable severity. Onset common <5 years

Treatment: TNF inhibitor, hematopoietic stem cell transplantation, IL6 receptor antibody (tocilizumab)

Non-genetic confirmatory test: plasma ADA2 enzyme activity
Sources: Literature
BabyScreen+ newborn screening v0.1250 IL7R Zornitza Stark Marked gene: IL7R as ready
BabyScreen+ newborn screening v0.1250 IL2RG Zornitza Stark Marked gene: IL2RG as ready
BabyScreen+ newborn screening v0.1250 IKBKG Zornitza Stark Marked gene: IKBKG as ready
BabyScreen+ newborn screening v0.1248 IGSF1 Zornitza Stark Marked gene: IGSF1 as ready
BabyScreen+ newborn screening v0.1248 IGSF1 Zornitza Stark Phenotypes for gene: IGSF1 were changed from Central hypothyroidism and testicular enlargement to Hypothyroidism, central, and testicular enlargement, MIM# 300888
BabyScreen+ newborn screening v0.1247 IGSF1 Zornitza Stark reviewed gene: IGSF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypothyroidism, central, and testicular enlargement, MIM# 300888; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1247 IGLL1 Zornitza Stark Marked gene: IGLL1 as ready
BabyScreen+ newborn screening v0.1247 IGHMBP2 Zornitza Stark Marked gene: IGHMBP2 as ready
BabyScreen+ newborn screening v0.1247 IGHMBP2 Zornitza Stark Phenotypes for gene: IGHMBP2 were changed from Spinal muscular atrophy with respiratory distress to Neuronopathy, distal hereditary motor, type VI, MIM# 604320; Charcot-Marie-Tooth disease, axonal, type 2S, MIM# 616155
BabyScreen+ newborn screening v0.1245 IGHMBP2 Zornitza Stark reviewed gene: IGHMBP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, type VI, MIM# 604320, Charcot-Marie-Tooth disease, axonal, type 2S, MIM# 616155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1245 IGHM Zornitza Stark Marked gene: IGHM as ready
BabyScreen+ newborn screening v0.1245 IDUA Zornitza Stark Marked gene: IDUA as ready
BabyScreen+ newborn screening v0.1245 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from Mucopolysaccharidosis Ih, MIM#607014 to Mucopolysaccharidosis type 1, MONDO:0001586
BabyScreen+ newborn screening v0.1244 IDUA Zornitza Stark reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type 1, MONDO:0001586; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1244 IDS Zornitza Stark Marked gene: IDS as ready
BabyScreen+ newborn screening v0.1244 IDS Zornitza Stark Phenotypes for gene: IDS were changed from Mucopolysaccharidosis II to Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900
BabyScreen+ newborn screening v0.1243 IDS Zornitza Stark reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1243 IL10RA Zornitza Stark Marked gene: IL10RA as ready
BabyScreen+ newborn screening v0.1243 IL10RA Zornitza Stark Phenotypes for gene: IL10RA were changed from Inflammatory bowel disease, MIM#613148 to Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148
BabyScreen+ newborn screening v0.1242 IL10RA Zornitza Stark reviewed gene: IL10RA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1242 INVS Zornitza Stark Marked gene: INVS as ready
BabyScreen+ newborn screening v0.1240 IQCB1 Zornitza Stark Marked gene: IQCB1 as ready
BabyScreen+ newborn screening v0.1238 IRAK4 Zornitza Stark Marked gene: IRAK4 as ready
BabyScreen+ newborn screening v0.1238 IRF6 Zornitza Stark Marked gene: IRF6 as ready
BabyScreen+ newborn screening v0.1236 ISPD Zornitza Stark Marked gene: ISPD as ready
BabyScreen+ newborn screening v0.1236 ISPD Zornitza Stark Phenotypes for gene: ISPD were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643 Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052
BabyScreen+ newborn screening v0.1234 ISPD Zornitza Stark reviewed gene: ISPD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643 Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1234 ITGA3 Zornitza Stark Marked gene: ITGA3 as ready
BabyScreen+ newborn screening v0.1233 ITGB2 Zornitza Stark Marked gene: ITGB2 as ready
BabyScreen+ newborn screening v0.1233 ITGB4 Zornitza Stark Marked gene: ITGB4 as ready
BabyScreen+ newborn screening v0.1230 IYD Zornitza Stark Marked gene: IYD as ready
BabyScreen+ newborn screening v0.1230 HK1 Zornitza Stark Marked gene: HK1 as ready
BabyScreen+ newborn screening v0.1227 JAK3 Zornitza Stark Marked gene: JAK3 as ready
BabyScreen+ newborn screening v0.1227 JAG1 Zornitza Stark Marked gene: JAG1 as ready
BabyScreen+ newborn screening v0.1225 KCNJ1 Zornitza Stark Marked gene: KCNJ1 as ready
BabyScreen+ newborn screening v0.1225 KCNJ1 Zornitza Stark Phenotypes for gene: KCNJ1 were changed from Bartter syndrome to Bartter syndrome, type 2, 241200
BabyScreen+ newborn screening v0.1224 KCNJ1 Zornitza Stark reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 2, 241200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1224 KCNA1 Zornitza Stark Marked gene: KCNA1 as ready
BabyScreen+ newborn screening v0.1222 KARS Zornitza Stark Marked gene: KARS as ready
BabyScreen+ newborn screening v0.1222 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1222 KARS Zornitza Stark Phenotypes for gene: KARS were changed from deafness with progressive leukodystrophy to Leukoencephalopathy with or without deafness (LEPID), MIM#619147; Deafness, autosomal recessive 89, MIM# 613916; Congenital deafness and adult-onset progressive leukoencephalopathy (DEAPLE), MIM#619196
BabyScreen+ newborn screening v0.1221 KARS Zornitza Stark Tag for review tag was added to gene: KARS.
BabyScreen+ newborn screening v0.1221 KARS Zornitza Stark reviewed gene: KARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukoencephalopathy with or without deafness (LEPID), MIM#619147, Deafness, autosomal recessive 89, MIM# 613916, Congenital deafness and adult-onset progressive leukoencephalopathy (DEAPLE), MIM#619196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1221 KANSL1 Zornitza Stark Marked gene: KANSL1 as ready
BabyScreen+ newborn screening v0.1219 KCNJ2 Zornitza Stark Marked gene: KCNJ2 as ready
BabyScreen+ newborn screening v0.1219 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from Andersen cardiodysrhythmic periodic paralysis to Andersen syndrome MIM#170390; Atrial fibrillation, familial, 9 MIM#613980; Short QT syndrome 3 MIM#609622
BabyScreen+ newborn screening v0.1217 KCNJ2 Zornitza Stark Tag for review tag was added to gene: KCNJ2.
Tag cardiac tag was added to gene: KCNJ2.
BabyScreen+ newborn screening v0.1217 KCNQ4 Zornitza Stark Marked gene: KCNQ4 as ready
BabyScreen+ newborn screening v0.1215 KBTBD13 Zornitza Stark Marked gene: KBTBD13 as ready
BabyScreen+ newborn screening v0.1215 KBTBD13 Zornitza Stark Phenotypes for gene: KBTBD13 were changed from Nemaline myopathy to Nemaline myopathy 6, autosomal dominant, MIM# 609273; Hereditary motor neuropathy late-onset; limb girdle muscular dystrophy
BabyScreen+ newborn screening v0.1212 KBTBD13 Zornitza Stark reviewed gene: KBTBD13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 6, autosomal dominant, MIM# 609273, Hereditary motor neuropathy late-onset, limb girdle muscular dystrophy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1212 KCNT1 Zornitza Stark Marked gene: KCNT1 as ready
BabyScreen+ newborn screening v0.1211 KCNT1 Zornitza Stark reviewed gene: KCNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 14, MIM# 614959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1211 KCTD7 Zornitza Stark Marked gene: KCTD7 as ready
BabyScreen+ newborn screening v0.1211 KCTD7 Zornitza Stark Phenotypes for gene: KCTD7 were changed from Epilepsy, progressive myoclonic to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726)
BabyScreen+ newborn screening v0.1209 KCTD7 Zornitza Stark reviewed gene: KCTD7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1209 HGSNAT Zornitza Stark Marked gene: HGSNAT as ready
BabyScreen+ newborn screening v0.1209 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from Mucopolysaccharidosis IIIC to Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930
BabyScreen+ newborn screening v0.1207 HGSNAT Zornitza Stark reviewed gene: HGSNAT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1207 HGF Zornitza Stark Marked gene: HGF as ready
BabyScreen+ newborn screening v0.1206 HEXB Zornitza Stark Marked gene: HEXB as ready
BabyScreen+ newborn screening v0.1204 HEXA Zornitza Stark Marked gene: HEXA as ready
BabyScreen+ newborn screening v0.1202 HDAC8 Zornitza Stark Marked gene: HDAC8 as ready
BabyScreen+ newborn screening v0.1202 HDAC8 Zornitza Stark Phenotypes for gene: HDAC8 were changed from Cornelia de Lange syndrome-like features, ocular hypertelorism & large fontanelle to Cornelia de Lange syndrome 5, MIM# 300882
BabyScreen+ newborn screening v0.1199 GJC2 Zornitza Stark Marked gene: GJC2 as ready
BabyScreen+ newborn screening v0.1199 GJC2 Zornitza Stark Phenotypes for gene: GJC2 were changed from Pelizaeus-Merzbacher-like disease to Spastic paraplegia 44, autosomal recessive MIM#613206; Leukodystrophy, hypomyelinating, 2 MIM#608804; Lymphatic malformation 3 MIM#613480
BabyScreen+ newborn screening v0.1196 GJC2 Zornitza Stark reviewed gene: GJC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 44, autosomal recessive MIM#613206, Leukodystrophy, hypomyelinating, 2 MIM#608804, Lymphatic malformation 3 MIM#613480; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1196 GJB1 Zornitza Stark Marked gene: GJB1 as ready
BabyScreen+ newborn screening v0.1196 GJB1 Zornitza Stark Phenotypes for gene: GJB1 were changed from Charcot-Marie-Tooth neuropathy to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800
BabyScreen+ newborn screening v0.1193 GJB1 Zornitza Stark reviewed gene: GJB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1193 GIF Zornitza Stark Marked gene: GIF as ready
BabyScreen+ newborn screening v0.1190 SLC16A1 Zornitza Stark reviewed gene: SLC16A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Monocarboxylate transporter 1 deficiency, MIM# 616095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1190 SLC13A5 Zornitza Stark Marked gene: SLC13A5 as ready
BabyScreen+ newborn screening v0.1190 TNFRSF11A Zornitza Stark Marked gene: TNFRSF11A as ready
BabyScreen+ newborn screening v0.1189 TNFRSF11B Zornitza Stark Marked gene: TNFRSF11B as ready
BabyScreen+ newborn screening v0.1186 TNFSF11 Zornitza Stark Marked gene: TNFSF11 as ready
BabyScreen+ newborn screening v0.1183 TNNI2 Zornitza Stark Marked gene: TNNI2 as ready
BabyScreen+ newborn screening v0.1183 TNNI2 Zornitza Stark Phenotypes for gene: TNNI2 were changed from Distal arthrogryposis syndrome 2b to Arthrogryposis, distal, type 2B1 MIM#601680
BabyScreen+ newborn screening v0.1180 TNNT1 Zornitza Stark Marked gene: TNNT1 as ready
BabyScreen+ newborn screening v0.1177 TNNT3 Zornitza Stark Marked gene: TNNT3 as ready
BabyScreen+ newborn screening v0.1177 TNNT3 Zornitza Stark Phenotypes for gene: TNNT3 were changed from Arthyrgryposis, distal to Arthrogryposis, distal MIM#618435
BabyScreen+ newborn screening v0.1174 TP53 Zornitza Stark Marked gene: TP53 as ready
BabyScreen+ newborn screening v0.1172 TPM2 Zornitza Stark Marked gene: TPM2 as ready
BabyScreen+ newborn screening v0.1172 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from Nemaline myopathy; Arthrogryposis multiplex congenita, distal to Arthrgryposis MIM#108120; Nemaline myopathy MIM#609285
BabyScreen+ newborn screening v0.1169 TPM3 Zornitza Stark Marked gene: TPM3 as ready
BabyScreen+ newborn screening v0.1166 SLC26A3 Seb Lunke Marked gene: SLC26A3 as ready
BabyScreen+ newborn screening v0.1166 SLC26A3 Seb Lunke Phenotypes for gene: SLC26A3 were changed from Chloride diarrhea, congenital, Finnish type to Diarrhoea 1, secretory chloride, congenital, MIM# 214700
BabyScreen+ newborn screening v0.1165 SLC26A3 Seb Lunke reviewed gene: SLC26A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diarrhoea 1, secretory chloride, congenital, MIM# 214700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1165 SLC26A2 Seb Lunke Marked gene: SLC26A2 as ready
BabyScreen+ newborn screening v0.1163 SLC25A4 Seb Lunke Marked gene: SLC25A4 as ready
BabyScreen+ newborn screening v0.1163 SLC25A4 Seb Lunke Phenotypes for gene: SLC25A4 were changed from Progressive external ophthalmoplegia to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418
BabyScreen+ newborn screening v0.1160 SLC25A4 Seb Lunke reviewed gene: SLC25A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1160 SLC16A1 Seb Lunke Marked gene: SLC16A1 as ready
BabyScreen+ newborn screening v0.1158 SLC16A1 Seb Lunke reviewed gene: SLC16A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301549; Phenotypes: Monocarboxylate transporter 1 deficiency, MIM# 616095; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1156 SLC25A38 Seb Lunke Marked gene: SLC25A38 as ready
BabyScreen+ newborn screening v0.1155 SLC25A20 Seb Lunke Marked gene: SLC25A20 as ready
BabyScreen+ newborn screening v0.1154 SLC25A20 Seb Lunke reviewed gene: SLC25A20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Carnitine-acylcarnitine translocase deficiency, MIM# 212138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1154 TNFRSF11A Lilian Downie changed review comment from: strong gene disease association
Infant onset osteopetrosis and immunodeficiency
No treatment



NB AD phenotype has later onset; to: strong gene disease association
Infant onset osteopetrosis and immunodeficiency
Treatment bone marrow transplant



NB AD phenotype has later onset
BabyScreen+ newborn screening v0.1154 TNFSF11 Lilian Downie changed review comment from: Strong gene disease association (gene also known as RANKL)
Infant, early childhood onset increased bone density, lack of bone marrow cavity, stunted growth, macrocephaly, progressive deafness, blindness, hepatosplenomegaly, and severe anemia.
No treatment; to: Strong gene disease association (gene also known as RANKL)
Infant, early childhood onset increased bone density, lack of bone marrow cavity, stunted growth, macrocephaly, progressive deafness, blindness, hepatosplenomegaly, and severe anemia.
No treatment
BabyScreen+ newborn screening v0.1154 TNNI2 Lilian Downie reviewed gene: TNNI2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34502093; Phenotypes: Arthrogryposis, distal, type 2B1 MIM#601680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1154 TNNT3 Lilian Downie reviewed gene: TNNT3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 19309503; Phenotypes: Arthrogryposis, distal MIM#618435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1154 TPM2 Lilian Downie reviewed gene: TPM2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 27726070; Phenotypes: Arthrgryposis MIM#108120, Nemaline myopathy MIM#609285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1154 HCFC1 John Christodoulou reviewed gene: HCFC1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301503, PMID: 26893841, PMID: 35337626; Phenotypes: nonimmune hydrops, cardiomyopathy, intrauterine growth restriction, microcephaly, global dev delay, ID, seizures; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1154 GUSB John Christodoulou reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31661765, PMID: 32063397; Phenotypes: facial dysmorphisms, skeletal deformities, cardiac valve involvement, ocular involvement, motor delay, developmental delay, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1154 GRHPR John Christodoulou reviewed gene: GRHPR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301742; Phenotypes: nephrolithiasis, haematuria, renal colic, obstruction of the urinary tract, Nephrocalcinosis, End-stage renal disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1154 GNS John Christodoulou reviewed gene: GNS: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31536183; Phenotypes: ID, Coarse facies, Thick hair and hirsutism, Hepatosplenomegaly, Joint stiffness, Hearing loss, Frequent upper-respiratory and ear infections, Inguinal and/or umbilical hernias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1154 GNPTG John Christodoulou reviewed gene: GNPTG: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301784; Phenotypes: Growth rate deceleration, Joint stiffness of the fingers, shoulders, and hips, Gradual mild coarsening of facial features, Genu valgum, scoliosis, hyperlordosis, mitral valve thickening; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1154 SLC25A19 Zornitza Stark Marked gene: SLC25A19 as ready
BabyScreen+ newborn screening v0.1151 COL11A1 Zornitza Stark changed review comment from: Mono-allelic variants in this gene cause Stickler syndrome, as well as isolated post-lingual deafness, and the rare Marshall syndrome.

There is some genotype-phenotype correlation.

Treatment: ocular surveillance and surgery to prevent retinal detachment

For review; to: Mono-allelic variants in this gene cause Stickler syndrome, as well as isolated post-lingual deafness, and the rare Marshall syndrome.

There is some genotype-phenotype correlation.

Treatment: ocular surveillance and surgery to prevent retinal detachment. Usually after age 2-3 years.

Discussed with ophthalmology: would start glaucoma surveillance in first year of life.
BabyScreen+ newborn screening v0.1151 COL2A1 Zornitza Stark changed review comment from: Variants in this gene are associated with a range of skeletal phenotypes.

Onset and severity can be variable.

Treatment: surveillance and prophylactic retinal laser treatment to prevent retinal detachment.

For review.; to: Variants in this gene are associated with a range of skeletal phenotypes.

Onset and severity can be variable.

Treatment: surveillance and prophylactic retinal laser treatment to prevent retinal detachment. This is usually after the age of 2-3 years.

Discussed with ophthalmology, would start glaucoma surveillance in the first year of life.
BabyScreen+ newborn screening v0.1151 SLC25A15 Seb Lunke Marked gene: SLC25A15 as ready
BabyScreen+ newborn screening v0.1150 SLC25A13 Seb Lunke Marked gene: SLC25A13 as ready
BabyScreen+ newborn screening v0.1148 SLC25A19 Seb Lunke gene: SLC25A19 was added
gene: SLC25A19 was added to gNBS. Sources: Literature
for review tags were added to gene: SLC25A19.
Mode of inheritance for gene: SLC25A19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A19 were set to 31095747
Phenotypes for gene: SLC25A19 were set to Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710
Review for gene: SLC25A19 was set to AMBER
Added comment: Established gene-disease association.

Onset of acute encephalopathic attacks in childhood (3 to 7 years) often after febrile illness, full recovery after attacks. Onset of chronic progressive polyneuropathy in late childhood.

Treatment: 5 patients treated with thiamine supplementation, which led to a substantial improvement in peripheral neuropathy and gait in early treated patients

Non-genetic confirmatory test: No
Sources: Literature
BabyScreen+ newborn screening v0.1147 HAX1 Zornitza Stark Marked gene: HAX1 as ready
BabyScreen+ newborn screening v0.1146 HARS2 Zornitza Stark Marked gene: HARS2 as ready
BabyScreen+ newborn screening v0.1146 HARS2 Zornitza Stark Gene: hars2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1146 HARS2 Zornitza Stark Phenotypes for gene: HARS2 were changed from Perrault syndrome; autosomal recessive sensorineural hearing loss to Perrault syndrome 2, MIM# 614926
BabyScreen+ newborn screening v0.1145 HARS2 Zornitza Stark Classified gene: HARS2 as Red List (low evidence)
BabyScreen+ newborn screening v0.1145 HARS2 Zornitza Stark Gene: hars2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1144 HARS2 Zornitza Stark reviewed gene: HARS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Perrault syndrome 2, MIM# 614926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1144 TRIM32 Zornitza Stark Marked gene: TRIM32 as ready
BabyScreen+ newborn screening v0.1144 TRIM32 Zornitza Stark Phenotypes for gene: TRIM32 were changed from Muscular dystrophy, limb-girdle, type 2H to Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
BabyScreen+ newborn screening v0.1141 TREX1 Zornitza Stark reviewed gene: TREX1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 1 MIM#225750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1141 TREX1 Zornitza Stark Marked gene: TREX1 as ready
BabyScreen+ newborn screening v0.1141 TREX1 Zornitza Stark Phenotypes for gene: TREX1 were changed from Aicardi-Goutieres syndrome 1 to Aicardi-Goutieres syndrome 1 MIM#225750
BabyScreen+ newborn screening v0.1138 TRAPPC2 Zornitza Stark Marked gene: TRAPPC2 as ready
BabyScreen+ newborn screening v0.1138 TRAPPC2 Zornitza Stark Phenotypes for gene: TRAPPC2 were changed from Spondyloepiphyseal dysplasia tarda to Spondyloepiphyseal dysplasia tarda MIM#313400
BabyScreen+ newborn screening v0.1135 TPP1 Zornitza Stark Marked gene: TPP1 as ready
BabyScreen+ newborn screening v0.1133 TPO Zornitza Stark Marked gene: TPO as ready
BabyScreen+ newborn screening v0.1132 HADH Zornitza Stark Marked gene: HADH as ready
BabyScreen+ newborn screening v0.1131 GOT2 Zornitza Stark Marked gene: GOT2 as ready
BabyScreen+ newborn screening v0.1131 GOT2 Zornitza Stark reviewed gene: GOT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 82, MIM# 618721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1131 GPC3 Zornitza Stark Marked gene: GPC3 as ready
BabyScreen+ newborn screening v0.1129 GPR143 Zornitza Stark Marked gene: GPR143 as ready
BabyScreen+ newborn screening v0.1129 GPR143 Zornitza Stark Phenotypes for gene: GPR143 were changed from Ocular albinism, type I to Ocular albinism, type I, Nettleship-Falls type, MIM# 300500
BabyScreen+ newborn screening v0.1127 GPR143 Zornitza Stark reviewed gene: GPR143: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ocular albinism, type I, Nettleship-Falls type, MIM# 300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1127 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
BabyScreen+ newborn screening v0.1125 GRHL2 Zornitza Stark Marked gene: GRHL2 as ready
BabyScreen+ newborn screening v0.1125 GRHL2 Zornitza Stark Phenotypes for gene: GRHL2 were changed from Autosomal dominant hearing loss, MIM# 608641 to Ectodermal dysplasia/short stature syndrome MIM#616029; Corneal dystrophy, posterior polymorphous, 4, MIM# 618031; Deafness, autosomal dominant 28, MIM# 608641
BabyScreen+ newborn screening v0.1122 GRHPR Zornitza Stark Phenotypes for gene: GRHPR were changed from Hyperoxaluria, primary, type II to Hyperoxaluria, primary, type II, MIM# 260000
BabyScreen+ newborn screening v0.1121 TRAPPC2 Lilian Downie reviewed gene: TRAPPC2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301324; Phenotypes: Spondyloepiphyseal dysplasia tarda MIM#313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1121 TREX1 Lilian Downie reviewed gene: TREX1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20301648, PMID: 32877590; Phenotypes: Aicardi-Goutieres syndrome 1 MIM#225750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1121 TRIM32 Lilian Downie reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21496629, PMID: 23142638; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1121 GRHPR Zornitza Stark Marked gene: GRHPR as ready
BabyScreen+ newborn screening v0.1121 GRHPR Zornitza Stark reviewed gene: GRHPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperoxaluria, primary, type II, MIM# 260000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1121 GRXCR1 Zornitza Stark Marked gene: GRXCR1 as ready
BabyScreen+ newborn screening v0.1121 GSS Zornitza Stark Marked gene: GSS as ready
BabyScreen+ newborn screening v0.1119 GUSB Zornitza Stark Marked gene: GUSB as ready
BabyScreen+ newborn screening v0.1119 GCM2 Zornitza Stark Marked gene: GCM2 as ready
BabyScreen+ newborn screening v0.1118 GCM2 Zornitza Stark gene: GCM2 was added
gene: GCM2 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: GCM2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GCM2 were set to 27745835; 20190276; 34967908; 35038313
Phenotypes for gene: GCM2 were set to Hyperparathyroidism 4, OMIM #617343; Hypoparathyroidism, familial isolated 2, OMIM #618883
Review for gene: GCM2 was set to GREEN
Added comment: Well established association. GoF for AD hyperparathyroidism, and LoF for AR hypoparathyroidism.

Variable age of onset.

Treatment for hypoPTH: calcium carbonate, calcitriol. HyperPTH: surgery?

Non-genetic confirmatory tests: calcium, phosphate, parathyroid hormone
Sources: Expert Review
BabyScreen+ newborn screening v0.1117 GUSB Zornitza Stark reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis VII, MIM# 253220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1117 GYS2 Zornitza Stark Marked gene: GYS2 as ready
BabyScreen+ newborn screening v0.1116 GNPTAB Zornitza Stark Marked gene: GNPTAB as ready
BabyScreen+ newborn screening v0.1114 GNE Zornitza Stark Marked gene: GNE as ready
BabyScreen+ newborn screening v0.1114 GNE Zornitza Stark Added comment: Comment when marking as ready: Check age of onset with neurology.
BabyScreen+ newborn screening v0.1111 GJA1 Zornitza Stark Marked gene: GJA1 as ready
BabyScreen+ newborn screening v0.1108 GIPC3 Zornitza Stark Marked gene: GIPC3 as ready
BabyScreen+ newborn screening v0.1108 GIPC3 Zornitza Stark Phenotypes for gene: GIPC3 were changed from Hearing loss to Deafness, autosomal recessive 15, MIM# 601869
BabyScreen+ newborn screening v0.1107 GLI3 Zornitza Stark Marked gene: GLI3 as ready
BabyScreen+ newborn screening v0.1105 CRLF1 Zornitza Stark Marked gene: CRLF1 as ready
BabyScreen+ newborn screening v0.1103 SLC19A2 Zornitza Stark Marked gene: SLC19A2 as ready
BabyScreen+ newborn screening v0.1103 SLC25A1 Seb Lunke Marked gene: SLC25A1 as ready
BabyScreen+ newborn screening v0.1101 SLC25A1 Seb Lunke reviewed gene: SLC25A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301347; Phenotypes: Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072, Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1101 SLC22A5 Seb Lunke Phenotypes for gene: SLC22A5 were changed from Carnitine deficiency, systemic primary, MIM#212140 to Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919
BabyScreen+ newborn screening v0.1099 SLC22A5 Seb Lunke reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22420015; Phenotypes: Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1099 SLC19A3 Seb Lunke Marked gene: SLC19A3 as ready
BabyScreen+ newborn screening v0.1097 SLC19A2 Seb Lunke Marked gene: SLC19A2 as ready
BabyScreen+ newborn screening v0.1095 SLC18A3 Seb Lunke Marked gene: SLC18A3 as ready
BabyScreen+ newborn screening v0.1094 SLC18A2 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset neurological condition.

Treatment: L-dopa resulted in severe exacerbation of the symptoms. Dopamine receptor agonist (pramipexole) resulted in improvement in symptoms. Earlier treatment more beneficial. Evidence from single family with benefits shown in 4 affected children.

Non-genetic confirmatory test: blood pressure measurement and sodium, potassium, aldosterone, renin levels; to: Established gene-disease association.

Childhood onset neurological condition.

Treatment: L-dopa resulted in severe exacerbation of the symptoms. Dopamine receptor agonist (pramipexole) resulted in improvement in symptoms. Earlier treatment more beneficial. Evidence from single family with benefits shown in 4 affected children.

Non-genetic confirmatory test: whole blood serotonin level
BabyScreen+ newborn screening v0.1094 SLC18A2 Seb Lunke Marked gene: SLC18A2 as ready
BabyScreen+ newborn screening v0.1094 SLC18A2 Seb Lunke Added comment: Comment when marking as ready: Is evidence for treatment sufficient?
BabyScreen+ newborn screening v0.1094 SLC18A2 Seb Lunke reviewed gene: SLC18A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23363473; Phenotypes: Parkinsonism-dystonia, infantile, 2, MIM# 618049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1094 KDM6A Zornitza Stark Marked gene: KDM6A as ready
BabyScreen+ newborn screening v0.1091 KIF21A Zornitza Stark Marked gene: KIF21A as ready
BabyScreen+ newborn screening v0.1091 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700of extraocular muscles, congenital to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
BabyScreen+ newborn screening v0.1090 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital to Fibrosis Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700of extraocular muscles, congenital
BabyScreen+ newborn screening v0.1088 KIF21A Zornitza Stark reviewed gene: KIF21A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1088 KIT Zornitza Stark Marked gene: KIT as ready
BabyScreen+ newborn screening v0.1086 KLF1 Zornitza Stark Marked gene: KLF1 as ready
BabyScreen+ newborn screening v0.1084 KLHL40 Zornitza Stark Marked gene: KLHL40 as ready
BabyScreen+ newborn screening v0.1082 KLHL41 Zornitza Stark Marked gene: KLHL41 as ready
BabyScreen+ newborn screening v0.1080 KAT6B Zornitza Stark Marked gene: KAT6B as ready
BabyScreen+ newborn screening v0.1080 KAT6B Zornitza Stark Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome to SBBYSS syndrome MIM #603736; Genitopatellar syndrome MIM #606170
BabyScreen+ newborn screening v0.1077 KAT6B Zornitza Stark reviewed gene: KAT6B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: SBBYSS syndrome MIM #603736, Genitopatellar syndrome MIM #606170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1077 KMT2D Zornitza Stark Marked gene: KMT2D as ready
BabyScreen+ newborn screening v0.1075 KRT14 Zornitza Stark Marked gene: KRT14 as ready
BabyScreen+ newborn screening v0.1075 KRT14 Zornitza Stark Phenotypes for gene: KRT14 were changed from Epidermolysis bullosa simplex to Epidermolysis bullosa simplex, recessive 1, 601001; Dermatopathia pigmentosa reticularis, 125595; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Koebner type, 131900; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000
BabyScreen+ newborn screening v0.1072 KRT14 Zornitza Stark reviewed gene: KRT14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa simplex, recessive 1, 601001, Dermatopathia pigmentosa reticularis, 125595, Epidermolysis bullosa simplex, Dowling-Meara type, 131760, Epidermolysis bullosa simplex, Koebner type, 131900, Epidermolysis bullosa simplex, Weber-Cockayne type, 131800, Naegeli-Franceschetti-Jadassohn syndrome, 161000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1072 KRT16 Zornitza Stark Marked gene: KRT16 as ready
BabyScreen+ newborn screening v0.1072 KRT16 Zornitza Stark Phenotypes for gene: KRT16 were changed from Pachyonychia congenita to Palmoplantar keratoderma, nonepidermolytic, focal (MIM#613000) Pachyonychia congenita 1 (MIM#167200)
BabyScreen+ newborn screening v0.1070 KRT16 Zornitza Stark reviewed gene: KRT16: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Palmoplantar keratoderma, nonepidermolytic, focal (MIM#613000) Pachyonychia congenita 1 (MIM#167200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1070 KRT17 Zornitza Stark Marked gene: KRT17 as ready
BabyScreen+ newborn screening v0.1068 KRT5 Zornitza Stark Marked gene: KRT5 as ready
BabyScreen+ newborn screening v0.1068 KRT5 Zornitza Stark Phenotypes for gene: KRT5 were changed from Epidermolysis bullosa simplex to Dowling-Degos disease 1, MIM# 179850; Epidermolysis bullosa simplex-MCR, MIM# 609352; Epidermolysis bullosa simplex-MP 131960; Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760; Epidermolysis bullosa simplex, Koebner type, MIM# 131900; Epidermolysis bullosa simplex, recessive 1, MIM# 601001; Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800
BabyScreen+ newborn screening v0.1065 KRT5 Zornitza Stark reviewed gene: KRT5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dowling-Degos disease 1, MIM# 179850, Epidermolysis bullosa simplex-MCR, MIM# 609352, Epidermolysis bullosa simplex-MP 131960, Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760, Epidermolysis bullosa simplex, Koebner type, MIM# 131900, Epidermolysis bullosa simplex, recessive 1, MIM# 601001, Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1065 KRT6A Zornitza Stark Marked gene: KRT6A as ready
BabyScreen+ newborn screening v0.1063 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
BabyScreen+ newborn screening v0.1061 KRAS Zornitza Stark Marked gene: KRAS as ready
BabyScreen+ newborn screening v0.1061 KRAS Zornitza Stark Phenotypes for gene: KRAS were changed from Noonan syndrome to Cardiofaciocutaneous syndrome 2, MIM# 615278; Noonan syndrome 3, MIM# 609942
BabyScreen+ newborn screening v0.1059 KRAS Zornitza Stark reviewed gene: KRAS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiofaciocutaneous syndrome 2, MIM# 615278, Noonan syndrome 3, MIM# 609942; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1059 HRAS Zornitza Stark Marked gene: HRAS as ready
BabyScreen+ newborn screening v0.1057 HINT1 Zornitza Stark Marked gene: HINT1 as ready
BabyScreen+ newborn screening v0.1057 HINT1 Zornitza Stark Phenotypes for gene: HINT1 were changed from Axonal neuropathy with neuromyotonia to Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200; Gamstorp-Wohlfart syndrome, MONDO:0007646
BabyScreen+ newborn screening v0.1055 HINT1 Zornitza Stark reviewed gene: HINT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200, Gamstorp-Wohlfart syndrome, MONDO:0007646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1055 FAM126A Zornitza Stark Marked gene: FAM126A as ready
BabyScreen+ newborn screening v0.1055 FAM126A Zornitza Stark Phenotypes for gene: FAM126A were changed from Hypomyelination and congenital cataract to Hypomyelinating leukodystrophy 5 MONDO:0012514
BabyScreen+ newborn screening v0.1052 BMPR1A Zornitza Stark changed review comment from: Well established gene-disease association.

Polyposis: onset in childhood although cancer onset tends to be in adulthood.

For review.; to: Well established gene-disease association.

Polyposis: onset in childhood although cancer onset tends to be in adulthood.

Screening typically starts in adolescence.
BabyScreen+ newborn screening v0.1052 CASQ2 Zornitza Stark Tag cardiac tag was added to gene: CASQ2.
BabyScreen+ newborn screening v0.1051 DDB2 Zornitza Stark changed review comment from: Established gene-disease association.

Range of age of onset, from childhood to adulthood. Most reported patients are adults, and this subtype which is generally milder.

Treatment: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.

For review re age of onset.; to: Established gene-disease association.

Range of age of onset, from childhood to adulthood. Most reported patients are adults, and this subtype which is generally milder.

Treatment: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.
BabyScreen+ newborn screening v0.1051 ERCC5 Zornitza Stark changed review comment from: Bi-allelic variants cause a range of DNA repair disorders.

Variable severity and age of onset of manifestations.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.

For discussion.; to: Bi-allelic variants cause a range of DNA repair disorders.

Variable severity and age of onset of manifestations.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.
BabyScreen+ newborn screening v0.1049 TSC2 Zornitza Stark changed review comment from: Treatment is largely symptomatic.; to: Treatment is symptomatic.
BabyScreen+ newborn screening v0.1047 ERCC2 Zornitza Stark changed review comment from: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE.

DNA repair disorder.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.

For discussion.; to: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE.

DNA repair disorder.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.
BabyScreen+ newborn screening v0.1044 FAM161A Zornitza Stark Marked gene: FAM161A as ready
BabyScreen+ newborn screening v0.1042 FAM20C Zornitza Stark Marked gene: FAM20C as ready
BabyScreen+ newborn screening v0.1040 FAM58A Zornitza Stark Marked gene: FAM58A as ready
BabyScreen+ newborn screening v0.1038 FANCA Zornitza Stark Marked gene: FANCA as ready
BabyScreen+ newborn screening v0.1037 FANCB Zornitza Stark Marked gene: FANCB as ready
BabyScreen+ newborn screening v0.1036 FANCC Zornitza Stark Marked gene: FANCC as ready
BabyScreen+ newborn screening v0.1035 FANCD2 Zornitza Stark Marked gene: FANCD2 as ready
BabyScreen+ newborn screening v0.1034 FANCG Zornitza Stark Marked gene: FANCG as ready
BabyScreen+ newborn screening v0.1034 FANCI Zornitza Stark Marked gene: FANCI as ready
BabyScreen+ newborn screening v0.1034 FAS Zornitza Stark Marked gene: FAS as ready
BabyScreen+ newborn screening v0.1033 FBN1 Zornitza Stark Marked gene: FBN1 as ready
BabyScreen+ newborn screening v0.1033 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from Marfan's syndrome; Weill-Marchesani syndrome 2, dominant; Shprintzen-Goldberg syndrome to Marfan syndrome, MIM# 154700
BabyScreen+ newborn screening v0.1031 FBN1 Zornitza Stark reviewed gene: FBN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Marfan syndrome, MIM# 154700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1031 GDAP1 Zornitza Stark Marked gene: GDAP1 as ready
BabyScreen+ newborn screening v0.1031 GDAP1 Zornitza Stark Phenotypes for gene: GDAP1 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, axonal, type 2K, MIM#607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM#607706; Charcot-Marie-Tooth disease, recessive intermediate, A, MIM#608340; Charcot-Marie-Tooth disease, type 4A, MIM#214400
BabyScreen+ newborn screening v0.1027 FERMT3 Zornitza Stark Marked gene: FERMT3 as ready
BabyScreen+ newborn screening v0.1027 FGA Zornitza Stark Marked gene: FGA as ready
BabyScreen+ newborn screening v0.1026 FGB Zornitza Stark Marked gene: FGB as ready
BabyScreen+ newborn screening v0.1025 FGD1 Zornitza Stark Marked gene: FGD1 as ready
BabyScreen+ newborn screening v0.1025 FGD1 Zornitza Stark Phenotypes for gene: FGD1 were changed from Aarskog-Scott syndrome to Aarskog-Scott syndrome, MIM # 305400; Mental retardation, X-linked syndromic 16, MIM# 305400
BabyScreen+ newborn screening v0.1023 FGD1 Zornitza Stark reviewed gene: FGD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aarskog-Scott syndrome, MIM # 305400, Mental retardation, X-linked syndromic 16, MIM# 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1023 FGD4 Zornitza Stark Marked gene: FGD4 as ready
BabyScreen+ newborn screening v0.1023 FGD4 Zornitza Stark Phenotypes for gene: FGD4 were changed from Charcot-Marie-Tooth disease to Charcot Marie Tooth disease, type 4H, MIM#609311
BabyScreen+ newborn screening v0.1021 FGD4 Zornitza Stark reviewed gene: FGD4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot Marie Tooth disease, type 4H, MIM#609311; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1021 FGF3 Zornitza Stark Marked gene: FGF3 as ready
BabyScreen+ newborn screening v0.1021 FGF3 Zornitza Stark Phenotypes for gene: FGF3 were changed from Deafness, congenital with inner ear agenesis, microtia, and microdontia to Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706
BabyScreen+ newborn screening v0.1020 FGF3 Zornitza Stark reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1020 FBN2 Zornitza Stark Marked gene: FBN2 as ready
BabyScreen+ newborn screening v0.1019 FBN2 Zornitza Stark reviewed gene: FBN2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Contractural arachnodactyly, congenital, MIM# 121050; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1019 SLC34A3 Zornitza Stark Marked gene: SLC34A3 as ready
BabyScreen+ newborn screening v0.1018 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
BabyScreen+ newborn screening v0.1018 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from Kallmann syndrome to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Jackson-Weiss syndrome 123150; Osteoglophonic dysplasia 166250; Pfeiffer syndrome 101600; Trigonocephaly 1 190440
BabyScreen+ newborn screening v0.1016 FGFR1 Zornitza Stark reviewed gene: FGFR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Jackson-Weiss syndrome 123150, Osteoglophonic dysplasia 166250, Pfeiffer syndrome 101600, Trigonocephaly 1 190440; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1016 FGFR2 Zornitza Stark Marked gene: FGFR2 as ready
BabyScreen+ newborn screening v0.1016 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from Jackson-Weiss syndrome; Apert syndrome; Crouzon syndrome; Pfeiffer syndrome; Beare-Stevenson cutis gyrata syndrome to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410; Apert syndrome, MIM# 101200; Beare-Stevenson cutis gyrata syndrome, MIM# 123790; Bent bone dysplasia syndrome, MIM# 614592; Craniofacial-skeletal-dermatologic dysplasia, MIM# 101600; Crouzon syndrome , MIM#123500; Jackson-Weiss syndrome,MIM# 123150; LADD syndrome, MIM# 149730; Pfeiffer syndrome,MIM# 101600; Saethre-Chotzen syndrome 101400
BabyScreen+ newborn screening v0.1014 FGFR2 Zornitza Stark reviewed gene: FGFR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592, Craniofacial-skeletal-dermatologic dysplasia, MIM# 101600, Crouzon syndrome , MIM#123500, Jackson-Weiss syndrome,MIM# 123150, LADD syndrome, MIM# 149730, Pfeiffer syndrome,MIM# 101600, Saethre-Chotzen syndrome 101400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1014 FGFR3 Zornitza Stark Marked gene: FGFR3 as ready
BabyScreen+ newborn screening v0.1012 FGG Zornitza Stark Marked gene: FGG as ready
BabyScreen+ newborn screening v0.1011 FKRP Zornitza Stark Marked gene: FKRP as ready
BabyScreen+ newborn screening v0.1011 FKRP Zornitza Stark Phenotypes for gene: FKRP were changed from Muscle-eye-brain disease; Muscular dystrophy, limb girdle 2I to Muscular dystrophy-dystroglycanopathy MONDO:0018276
BabyScreen+ newborn screening v0.1009 FKRP Zornitza Stark reviewed gene: FKRP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1009 FKTN Zornitza Stark Marked gene: FKTN as ready
BabyScreen+ newborn screening v0.1009 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from Muscular dystrophy, Fukuyama; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies to Muscular dystrophy-dystroglycanopathy MONDO:0018276
BabyScreen+ newborn screening v0.1007 FKTN Zornitza Stark reviewed gene: FKTN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1007 FLCN Zornitza Stark changed review comment from: Well established gene-disease association.

Typically manifests in adulthood, therefore predictive testing usually offered in adolescence with surveillance thereafter.

For review.; to: Well established gene-disease association.

Typically manifests in adulthood, therefore predictive testing usually offered in adolescence with surveillance thereafter. Renal cancer age of onset ~50 years.

For review.
BabyScreen+ newborn screening v0.1007 FLCN Zornitza Stark Marked gene: FLCN as ready
BabyScreen+ newborn screening v0.1005 FLNA Zornitza Stark Marked gene: FLNA as ready
BabyScreen+ newborn screening v0.1003 FOXA2 Zornitza Stark Marked gene: FOXA2 as ready
BabyScreen+ newborn screening v0.1003 FOXA2 Zornitza Stark Phenotypes for gene: FOXA2 were changed from Combined pituitary hormone deficiencies, genetic forms, ORPHA:95494; Congenital isolated hyperinsulinism, ORPHA:657 to Hyperinsulinism MONDO:0002177
BabyScreen+ newborn screening v0.1001 FOXC1 Zornitza Stark Marked gene: FOXC1 as ready
BabyScreen+ newborn screening v0.999 FOXC2 Zornitza Stark Marked gene: FOXC2 as ready
BabyScreen+ newborn screening v0.999 FOXC2 Zornitza Stark Phenotypes for gene: FOXC2 were changed from Lymphoedema, primary to Lymphoedema-distichiasis syndrome, MIM# 153400
BabyScreen+ newborn screening v0.997 FOXF1 Zornitza Stark Marked gene: FOXF1 as ready
BabyScreen+ newborn screening v0.997 FOXF1 Zornitza Stark Phenotypes for gene: FOXF1 were changed from Alveolar capillary dysplasia with misalignment of pulmonary veins to Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380
BabyScreen+ newborn screening v0.995 FOXF1 Zornitza Stark reviewed gene: FOXF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.995 FOXI1 Zornitza Stark Marked gene: FOXI1 as ready
BabyScreen+ newborn screening v0.995 FOXI1 Zornitza Stark Phenotypes for gene: FOXI1 were changed from sensorineural deafness and distal renal tubular acidosis to autosomal recessive distal renal tubular acidosis MONDO:0018440
BabyScreen+ newborn screening v0.993 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.993 FOXP3 Zornitza Stark Marked gene: FOXP3 as ready
BabyScreen+ newborn screening v0.992 FRAS1 Zornitza Stark Marked gene: FRAS1 as ready
BabyScreen+ newborn screening v0.990 GLDC Zornitza Stark Marked gene: GLDC as ready
BabyScreen+ newborn screening v0.987 GLB1 Zornitza Stark Marked gene: GLB1 as ready
BabyScreen+ newborn screening v0.987 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from Gangliosidosis GM1 to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010
BabyScreen+ newborn screening v0.984 GLB1 Zornitza Stark reviewed gene: GLB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: GM1-gangliosidosis, type I MIM#230500, GM1-gangliosidosis, type II MIM# 230600, GM1-gangliosidosis, type III MIM#230650, Mucopolysaccharidosis type IVB (Morquio) MIM#253010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.984 F10 Zornitza Stark Marked gene: F10 as ready
BabyScreen+ newborn screening v0.983 FTL Zornitza Stark Marked gene: FTL as ready
BabyScreen+ newborn screening v0.981 FXN Zornitza Stark Marked gene: FXN as ready
BabyScreen+ newborn screening v0.979 EZH2 Zornitza Stark Marked gene: EZH2 as ready
BabyScreen+ newborn screening v0.977 EYA4 Zornitza Stark Marked gene: EYA4 as ready
BabyScreen+ newborn screening v0.975 EYA1 Zornitza Stark Marked gene: EYA1 as ready
BabyScreen+ newborn screening v0.975 EYA1 Zornitza Stark Phenotypes for gene: EYA1 were changed from Branchiootorenal syndrome to Anterior segment anomalies with or without cataract MIM#602588; Branchiootic syndrome 1 MIM#602588; Branchiootorenal syndrome 1, with or without cataracts MIM#113650
BabyScreen+ newborn screening v0.973 EYA1 Zornitza Stark reviewed gene: EYA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Anterior segment anomalies with or without cataract MIM#602588, Branchiootic syndrome 1 MIM#602588, Branchiootorenal syndrome 1, with or without cataracts MIM#113650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.973 EXT2 Zornitza Stark Marked gene: EXT2 as ready
BabyScreen+ newborn screening v0.970 EXT1 Zornitza Stark Marked gene: EXT1 as ready
BabyScreen+ newborn screening v0.968 EVC2 Zornitza Stark Marked gene: EVC2 as ready
BabyScreen+ newborn screening v0.965 EVC Zornitza Stark Marked gene: EVC as ready
BabyScreen+ newborn screening v0.962 ESRRB Zornitza Stark Marked gene: ESRRB as ready
BabyScreen+ newborn screening v0.962 ESRRB Zornitza Stark Phenotypes for gene: ESRRB were changed from Hearing loss to Deafness, autosomal recessive 35, MIM#608565
BabyScreen+ newborn screening v0.961 ESPN Zornitza Stark Marked gene: ESPN as ready
BabyScreen+ newborn screening v0.961 ESCO2 Zornitza Stark Marked gene: ESCO2 as ready
BabyScreen+ newborn screening v0.961 ESCO2 Zornitza Stark Phenotypes for gene: ESCO2 were changed from Roberts syndrome to Juberg-Hayward syndrome, MIM# 216100; Roberts-SC phocomelia syndrome, MIM#268300
BabyScreen+ newborn screening v0.959 ESCO2 Zornitza Stark reviewed gene: ESCO2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Juberg-Hayward syndrome, MIM# 216100, Roberts-SC phocomelia syndrome, MIM#268300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.959 ERCC8 Zornitza Stark Marked gene: ERCC8 as ready
BabyScreen+ newborn screening v0.957 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
BabyScreen+ newborn screening v0.955 ERCC5 Zornitza Stark Marked gene: ERCC5 as ready
BabyScreen+ newborn screening v0.953 ERCC2 Zornitza Stark Marked gene: ERCC2 as ready
BabyScreen+ newborn screening v0.951 EPS8L2 Zornitza Stark Marked gene: EPS8L2 as ready
BabyScreen+ newborn screening v0.950 GLDC John Christodoulou changed review comment from: causes nonketotic hyperglycaemia

classical form presents in the neonatal period and treatments (eg sodium benzoate and NDMA receptor antagonists) do not alter the neurological trajectory

milder forms of the disorder (later onset, but still in early childhood), may show response to therapy (PMID: 21411353); potentially aided by phenotype-genotype correlations (PMID: 32421718); to: causes nonketotic hyperglycaemia

classical form presents in the neonatal period and treatments (eg sodium benzoate and NDMA receptor antagonists) do not alter the neurological trajectory

milder forms of the disorder (later onset, but still in early childhood), may show response to therapy (PMID: 21411353); potentially aided by phenotype-genotype correlations (PMID: 32421718)
BabyScreen+ newborn screening v0.950 GLB1 John Christodoulou reviewed gene: GLB1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34539759; Phenotypes: neurodegeneration, coarse facial features, gingival hyperplasia, cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.950 GLA John Christodoulou reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30017653; Phenotypes: neuropathic pain, cardiomyopathy, cataract, agniokeratomata, deafness, hypohidrosis, stroke, renal failure; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.950 GGCX John Christodoulou edited their review of gene: GGCX: Changed phenotypes: bleeding disorder, pseudoxanthoma elasticum, pigmentary retinopathy, congenital heart disease
BabyScreen+ newborn screening v0.950 EPS8 Zornitza Stark Marked gene: EPS8 as ready
BabyScreen+ newborn screening v0.950 EPS8 Zornitza Stark Phenotypes for gene: EPS8 were changed from deafness MIM#600205 to Autosomal recessive nonsyndromic hearing loss 102, MIM#600205, MONDO:0014428
BabyScreen+ newborn screening v0.949 EPS8 Zornitza Stark reviewed gene: EPS8: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Autosomal recessive nonsyndromic hearing loss 102, MIM# MONDO:0014428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.949 EPM2A Zornitza Stark Marked gene: EPM2A as ready
BabyScreen+ newborn screening v0.947 ENPP1 Zornitza Stark Marked gene: ENPP1 as ready
BabyScreen+ newborn screening v0.947 ENPP1 Zornitza Stark Phenotypes for gene: ENPP1 were changed from Arterial calcification, generalized, of infancy, 1 to Arterial calcification, generalized, of infancy, 1, MIM# 208000; Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312
BabyScreen+ newborn screening v0.946 ENPP1 Zornitza Stark changed review comment from: Bi-allelic variants:
GACI: well established gene-disease association, multiple families and mouse models.

Hypophosphataemic rickets: multiple families reported, some with features of GACI.

Reported variants are spread throughout the phosphodiesterase catalytic domain and nuclease-like domain. No genotype-phenotype correlation, variability even within the same family. These likely represent a spectrum of a single disorder, rather than two distinct disorders.

Should be able to distinguish clinically.

Treatment: etidronate, anti-hypertensive, calcitriol and oral phosphate supplements; to: Bi-allelic variants:
GACI: well established gene-disease association, multiple families and mouse models.

Hypophosphataemic rickets: multiple families reported, some with features of GACI.

Reported variants are spread throughout the phosphodiesterase catalytic domain and nuclease-like domain. No genotype-phenotype correlation, variability even within the same family. These likely represent a spectrum of a single disorder, rather than two distinct disorders.

Should be able to distinguish clinically.

Onset is congenital/early infancy.

Treatment: etidronate, anti-hypertensive, calcitriol and oral phosphate supplements
BabyScreen+ newborn screening v0.946 ENPP1 Zornitza Stark reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial calcification, generalized, of infancy, 1, MIM# 208000, Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.946 TTC7A Zornitza Stark Marked gene: TTC7A as ready
BabyScreen+ newborn screening v0.944 TTC37 Zornitza Stark Marked gene: TTC37 as ready
BabyScreen+ newborn screening v0.941 TTC21B Zornitza Stark Marked gene: TTC21B as ready
BabyScreen+ newborn screening v0.938 TSR2 Zornitza Stark Marked gene: TSR2 as ready
BabyScreen+ newborn screening v0.936 TSHR Zornitza Stark Marked gene: TSHR as ready
BabyScreen+ newborn screening v0.933 TSHB Zornitza Stark Marked gene: TSHB as ready
BabyScreen+ newborn screening v0.931 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
BabyScreen+ newborn screening v0.931 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from Pontocerebellar hypoplasia type 4 to Pontocerebellar hypoplasia type 2A MIM#277470
BabyScreen+ newborn screening v0.928 TSC2 Zornitza Stark Marked gene: TSC2 as ready
BabyScreen+ newborn screening v0.927 TSC1 Zornitza Stark Marked gene: TSC1 as ready
BabyScreen+ newborn screening v0.926 TRPM4 Zornitza Stark Marked gene: TRPM4 as ready
BabyScreen+ newborn screening v0.926 TRPM4 Zornitza Stark Phenotypes for gene: TRPM4 were changed from Cardiac conduction disease to Progressive familial heart block, type IB 604559
BabyScreen+ newborn screening v0.923 TRMU Zornitza Stark Marked gene: TRMU as ready
BabyScreen+ newborn screening v0.921 TRIOBP Zornitza Stark Marked gene: TRIOBP as ready
BabyScreen+ newborn screening v0.919 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
BabyScreen+ newborn screening v0.914 ENG Zornitza Stark changed review comment from: Well established gene disease association.

Clingen: strong actionability in adults
Although HHT is a developmental disorder and infants are occasionally severely affected, in most people the features are age-dependent and the diagnosis is not suspected until adolescence or later. The average age of onset for epistaxis is 12 years, with 50-80% of patients affected before the age of 20 and 78-96% developing it eventually. Most patients report the appearance of telangiectasia of the mouth, face, or hands 5-30 years after the onset of nose bleeds, most commonly during the third decade. GI bleeding, when present, usually presents in the 5th or 6th decades of life. Patients rarely develop significant GI bleeding before 40 years of age. Women are affected with GI bleeding in a ratio of 2-3:1. AVMs of the brain are typically present at birth, whereas those in the lung and liver typically develop over time. Hemorrhage is often the presenting symptom of cerebral AVMs, while visceral AVMs may cause transient ischemic attacks, embolic stroke, and cerebral or other abscesses. Hepatic AVMs can present as high-output heart failure, portal hypertension, or biliary disease.

However, screening guidelines recommend screening for cerebral AVMs in first 6 months of life or at diagnosis (MRI).

For review.; to: Well established gene disease association.

Clingen: strong actionability in adults
Although HHT is a developmental disorder and infants are occasionally severely affected, in most people the features are age-dependent and the diagnosis is not suspected until adolescence or later. The average age of onset for epistaxis is 12 years, with 50-80% of patients affected before the age of 20 and 78-96% developing it eventually. Most patients report the appearance of telangiectasia of the mouth, face, or hands 5-30 years after the onset of nose bleeds, most commonly during the third decade. GI bleeding, when present, usually presents in the 5th or 6th decades of life. Patients rarely develop significant GI bleeding before 40 years of age. Women are affected with GI bleeding in a ratio of 2-3:1. AVMs of the brain are typically present at birth, whereas those in the lung and liver typically develop over time. Hemorrhage is often the presenting symptom of cerebral AVMs, while visceral AVMs may cause transient ischemic attacks, embolic stroke, and cerebral or other abscesses. Hepatic AVMs can present as high-output heart failure, portal hypertension, or biliary disease.

However, screening guidelines recommend screening for cerebral AVMs in first 6 months of life or at diagnosis (MRI). Management guidelines also suggest screening in asymptomatic children for pulmonary AVMs, PMID 32894695.
BabyScreen+ newborn screening v0.914 ENG Zornitza Stark Marked gene: ENG as ready
BabyScreen+ newborn screening v0.914 ENG Zornitza Stark Phenotypes for gene: ENG were changed from Telangiectasia, hereditary hemorrhagic, type 1 to Telangiectasia, hereditary hemorrhagic, type 1 MIM#187300
BabyScreen+ newborn screening v0.912 ENG Zornitza Stark reviewed gene: ENG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 1 MIM#187300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.912 EMD Zornitza Stark Marked gene: EMD as ready
BabyScreen+ newborn screening v0.912 EMD Zornitza Stark Phenotypes for gene: EMD were changed from Muscular dystrophy, Emery-Dreifuss to Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300
BabyScreen+ newborn screening v0.910 EMD Zornitza Stark reviewed gene: EMD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.910 ELP1 Zornitza Stark Marked gene: ELP1 as ready
BabyScreen+ newborn screening v0.907 ELN Zornitza Stark Marked gene: ELN as ready
BabyScreen+ newborn screening v0.907 ELN Zornitza Stark Phenotypes for gene: ELN were changed from Supravalvar aortic stenosis to cutis laxa, autosomal dominant 1 MONDO:0007411; supravalvular aortic stenosis MONDO:0008504
BabyScreen+ newborn screening v0.905 ELN Zornitza Stark reviewed gene: ELN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: cutis laxa, autosomal dominant 1 MONDO:0007411, supravalvular aortic stenosis MONDO:0008504; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.905 ELANE Zornitza Stark Marked gene: ELANE as ready
BabyScreen+ newborn screening v0.904 EIF2AK3 Zornitza Stark Marked gene: EIF2AK3 as ready
BabyScreen+ newborn screening v0.904 EGR2 Zornitza Stark Marked gene: EGR2 as ready
BabyScreen+ newborn screening v0.904 EGR2 Zornitza Stark Phenotypes for gene: EGR2 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 1D 607678; Dejerine-Sottas disease 145900; Hypomyelinating neuropathy, congenital, 1, MIM# 605253
BabyScreen+ newborn screening v0.901 EGR2 Zornitza Stark reviewed gene: EGR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 1D 607678, Dejerine-Sottas disease 145900, Hypomyelinating neuropathy, congenital, 1 605253 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.901 EFTUD2 Zornitza Stark Marked gene: EFTUD2 as ready
BabyScreen+ newborn screening v0.900 EFL1 Zornitza Stark Marked gene: EFL1 as ready
BabyScreen+ newborn screening v0.900 EDNRB Zornitza Stark Marked gene: EDNRB as ready
BabyScreen+ newborn screening v0.900 EDNRB Zornitza Stark reviewed gene: EDNRB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome type 4A MONDO:0010192; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.900 EDN3 Zornitza Stark Marked gene: EDN3 as ready
BabyScreen+ newborn screening v0.900 EDN3 Zornitza Stark Phenotypes for gene: EDN3 were changed from Waardenburg syndrome to Waardenburg syndrome, type 4B, MIM# 613265
BabyScreen+ newborn screening v0.899 EDN3 Zornitza Stark reviewed gene: EDN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome, type 4B, MIM# 613265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.899 EDARADD Zornitza Stark Marked gene: EDARADD as ready
BabyScreen+ newborn screening v0.899 EDARADD Zornitza Stark Gene: edaradd has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.899 EDARADD Zornitza Stark Phenotypes for gene: EDARADD were changed from Ectodermal dysplasia, hypohidrotic to autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619
BabyScreen+ newborn screening v0.898 EDARADD Zornitza Stark Mode of inheritance for gene: EDARADD was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.897 EDARADD Zornitza Stark Classified gene: EDARADD as Red List (low evidence)
BabyScreen+ newborn screening v0.897 EDARADD Zornitza Stark Gene: edaradd has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.896 EDARADD Zornitza Stark reviewed gene: EDARADD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.896 EDAR Zornitza Stark Marked gene: EDAR as ready
BabyScreen+ newborn screening v0.896 EDAR Zornitza Stark Gene: edar has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.896 EDAR Zornitza Stark Phenotypes for gene: EDAR were changed from Ectodermal dysplasia, hypohidrotic to autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619
BabyScreen+ newborn screening v0.895 EDAR Zornitza Stark Classified gene: EDAR as Red List (low evidence)
BabyScreen+ newborn screening v0.895 EDAR Zornitza Stark Gene: edar has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.894 EDAR Zornitza Stark reviewed gene: EDAR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.894 EDA Zornitza Stark Marked gene: EDA as ready
BabyScreen+ newborn screening v0.892 DYSF Zornitza Stark Marked gene: DYSF as ready
BabyScreen+ newborn screening v0.892 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from Miyoshi muscular dystrophy 1; Muscular dystrophy, limb-girdle, type 2B to Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768
BabyScreen+ newborn screening v0.890 DYSF Zornitza Stark reviewed gene: DYSF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Miyoshi muscular dystrophy 1 254130, Muscular dystrophy, limb-girdle, autosomal recessive 2 253601, Myopathy, distal, with anterior tibial onset 606768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.890 DUOXA2 Zornitza Stark Marked gene: DUOXA2 as ready
BabyScreen+ newborn screening v0.890 TRPM4 Lilian Downie reviewed gene: TRPM4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 19726882, PMID: 33381229; Phenotypes: Progressive familial heart block, type IB 604559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.890 TSEN54 Lilian Downie reviewed gene: TSEN54: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301773; Phenotypes: Pontocerebellar hypoplasia type 2A MIM#277470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.890 DUOX2 Zornitza Stark Marked gene: DUOX2 as ready
BabyScreen+ newborn screening v0.889 DOK7 Zornitza Stark Marked gene: DOK7 as ready
BabyScreen+ newborn screening v0.889 DOCK8 Zornitza Stark Marked gene: DOCK8 as ready
BabyScreen+ newborn screening v0.889 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
BabyScreen+ newborn screening v0.888 DNM2 Zornitza Stark Marked gene: DNM2 as ready
BabyScreen+ newborn screening v0.888 DNM2 Zornitza Stark Phenotypes for gene: DNM2 were changed from Charcot-Marie-Tooth disease, axonal, type 2M; Myopathy, centronuclear to Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482 Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482
BabyScreen+ newborn screening v0.886 DNM2 Zornitza Stark reviewed gene: DNM2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482 Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.886 DNAJB6 Zornitza Stark Marked gene: DNAJB6 as ready
BabyScreen+ newborn screening v0.886 DNAJB6 Zornitza Stark Phenotypes for gene: DNAJB6 were changed from Muscular dystrophy, limb girdle to Muscular dystrophy, limb-girdle, autosomal dominant 1 MIM#603511
BabyScreen+ newborn screening v0.885 DNAJB6 Zornitza Stark reviewed gene: DNAJB6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 1 MIM#603511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.885 DNAI1 Zornitza Stark Marked gene: DNAI1 as ready
BabyScreen+ newborn screening v0.885 DNAI1 Zornitza Stark Phenotypes for gene: DNAI1 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400
BabyScreen+ newborn screening v0.883 DNAI1 Zornitza Stark reviewed gene: DNAI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.883 DNAH5 Zornitza Stark Marked gene: DNAH5 as ready
BabyScreen+ newborn screening v0.883 DNAH5 Zornitza Stark Phenotypes for gene: DNAH5 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644
BabyScreen+ newborn screening v0.881 DNAH5 Zornitza Stark reviewed gene: DNAH5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.881 DNAH11 Zornitza Stark Marked gene: DNAH11 as ready
BabyScreen+ newborn screening v0.881 DNAH11 Zornitza Stark Phenotypes for gene: DNAH11 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884
BabyScreen+ newborn screening v0.879 DNAH11 Zornitza Stark reviewed gene: DNAH11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.879 DNAAF1 Zornitza Stark Marked gene: DNAAF1 as ready
BabyScreen+ newborn screening v0.879 DNAAF1 Zornitza Stark Phenotypes for gene: DNAAF1 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 13, MIM# 613193
BabyScreen+ newborn screening v0.877 DNAAF1 Zornitza Stark reviewed gene: DNAAF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 13, MIM# 613193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.877 DMXL2 Zornitza Stark Marked gene: DMXL2 as ready
BabyScreen+ newborn screening v0.876 DMXL2 Zornitza Stark reviewed gene: DMXL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 81, MIM# 618663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.876 DMP1 Zornitza Stark Marked gene: DMP1 as ready
BabyScreen+ newborn screening v0.876 DMP1 Zornitza Stark Phenotypes for gene: DMP1 were changed from Hypophosphatemic rickets, AR to Hypophosphatemic rickets MIM#241520
BabyScreen+ newborn screening v0.875 DLL3 Zornitza Stark Marked gene: DLL3 as ready
BabyScreen+ newborn screening v0.873 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
BabyScreen+ newborn screening v0.870 DFNB59 Zornitza Stark Marked gene: DFNB59 as ready
BabyScreen+ newborn screening v0.870 DFNB59 Zornitza Stark Phenotypes for gene: DFNB59 were changed from Hearing loss to Deafness, autosomal recessive 59, MIM# 610220
BabyScreen+ newborn screening v0.869 DFNB59 Zornitza Stark commented on gene: DFNB59: DEFINITIVE by ClinGen, over 50 affected individuals from more than 10 families reported, supportive functional data including animal models.

New HGNC name is PJVK.

Hearing loss is pre-lingual, therefore include.

Treatment: hearing aids/cochlear implant.
BabyScreen+ newborn screening v0.869 DFNA5 Zornitza Stark Marked gene: DFNA5 as ready
BabyScreen+ newborn screening v0.869 DFNA5 Zornitza Stark Phenotypes for gene: DFNA5 were changed from Hearing loss to Deafness, autosomal dominant 5, MIM# 600994
BabyScreen+ newborn screening v0.867 GFAP Zornitza Stark changed review comment from: Clinical trial due to start in VIC. Age at entry is 2 years and older.; to: Clinical trial due to start in VIC. Age at entry is 2 years and older.

Keep on Amber list.
BabyScreen+ newborn screening v0.867 GFAP Zornitza Stark changed review comment from: Clinical trial due to start in VIC.; to: Clinical trial due to start in VIC. Age at entry is 2 years and older.
BabyScreen+ newborn screening v0.864 LAMA2 Zornitza Stark Tag pharmacogenomic tag was added to gene: LAMA2.
BabyScreen+ newborn screening v0.864 LAMA2 Zornitza Stark changed review comment from: No specific treatment.; to: No specific treatment.
Succinylcholine in induction of anaesthesia because of risk of hyperkalaemia and cardiac conduction abnormalities; statins, cholesterol-lowering medications, because of the risk of muscle damage.
BabyScreen+ newborn screening v0.864 DGUOK Zornitza Stark changed review comment from: Well established gene disease association.

Variable age of onset ranging from severe neonatal presentations to adult.

See comments below about treatment: emerging approaches.

For review.; to: Well established gene disease association.

Variable age of onset ranging from severe neonatal presentations to adult.

See comments below about treatment: emerging approaches. May not be eligible for liver transplant due to multi-system involvement.

For review.
BabyScreen+ newborn screening v0.864 DDB2 Zornitza Stark Marked gene: DDB2 as ready
BabyScreen+ newborn screening v0.862 ACVRL1 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable age of symptom onset and severity.

No specific treatment available.

However, management guidelines suggest screening in asymptomatic children for pulmonary AVMs, PMID 32894695.; to: Well established gene-disease association.

Variable age of symptom onset and severity.

No specific treatment available but emboli zing AVMs alters their natural history.

Management guidelines suggest screening in asymptomatic children for pulmonary AVMs, PMID 32894695.
BabyScreen+ newborn screening v0.862 PCBD1 Zornitza Stark changed review comment from: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.
; to: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.
BabyScreen+ newborn screening v0.862 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
BabyScreen+ newborn screening v0.861 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, MIM#610542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.861 GFM1 Zornitza Stark Marked gene: GFM1 as ready
BabyScreen+ newborn screening v0.859 GFAP Zornitza Stark Marked gene: GFAP as ready
BabyScreen+ newborn screening v0.857 PALB2 Zornitza Stark Marked gene: PALB2 as ready
BabyScreen+ newborn screening v0.856 DHCR7 Zornitza Stark changed review comment from: Well established gene-disease association.

Perinatal onset.

Cholesterol supplementation accepted as standard treatment. Questionable to what extent treatment improves outcomes. Not listed as treatable on rx-genes.

For review.; to: Well established gene-disease association.

Perinatal onset.

Cholesterol supplementation accepted as standard treatment. Questionable to what extent treatment improves outcomes but some improvement seen in metabolic parameters, and behavioural manifestations.
BabyScreen+ newborn screening v0.856 DHCR7 Zornitza Stark changed review comment from: Well established gene-disease association.

Perinatal onset.

Questionable to what extent treatment improves outcomes. Not listed as treatable on rx-genes.

For review.; to: Well established gene-disease association.

Perinatal onset.

Cholesterol supplementation accepted as standard treatment. Questionable to what extent treatment improves outcomes. Not listed as treatable on rx-genes.

For review.
BabyScreen+ newborn screening v0.851 GFPT1 Alison Yeung reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, MIM#610542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.851 GDAP1 Alison Yeung reviewed gene: GDAP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2K, MIM#607831, Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM#607706, Charcot-Marie-Tooth disease, recessive intermediate, A, MIM#608340, Charcot-Marie-Tooth disease, type 4A, MIM#214400; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.851 DMPK Zornitza Stark Marked gene: DMPK as ready
BabyScreen+ newborn screening v0.849 DCX Zornitza Stark Marked gene: DCX as ready
BabyScreen+ newborn screening v0.847 DCLRE1C Zornitza Stark Marked gene: DCLRE1C as ready
BabyScreen+ newborn screening v0.846 COL4A5 Zornitza Stark Marked gene: COL4A5 as ready
BabyScreen+ newborn screening v0.844 COL2A1 Zornitza Stark Marked gene: COL2A1 as ready
BabyScreen+ newborn screening v0.843 COL5A2 Zornitza Stark Marked gene: COL5A2 as ready
BabyScreen+ newborn screening v0.841 COL7A1 Zornitza Stark Marked gene: COL7A1 as ready
BabyScreen+ newborn screening v0.841 COL7A1 Zornitza Stark Phenotypes for gene: COL7A1 were changed from Epidermolysis bullosa dystrophica to EBD inversa, MIM# 226600; EBD, Bart type MIM# 132000 EBD, localisata variant; Epidermolysis bullosa dystrophica, MIM# 131750; Epidermolysis bullosa dystrophica, 226600; Epidermolysis bullosa pruriginosa 604129; Epidermolysis bullosa, pretibial, MIM# 131850; Transient bullous of the newborn 131705
BabyScreen+ newborn screening v0.838 COL7A1 Zornitza Stark reviewed gene: COL7A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: EBD inversa, MIM# 226600, EBD, Bart type MIM# 132000 EBD, localisata variant, Epidermolysis bullosa dystrophica, MIM# 131750, Epidermolysis bullosa dystrophica, 226600, Epidermolysis bullosa pruriginosa 604129, Epidermolysis bullosa, pretibial, MIM# 131850, Transient bullous of the newborn 131705; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.838 TWIST1 Zornitza Stark Marked gene: TWIST1 as ready
BabyScreen+ newborn screening v0.835 TWNK Zornitza Stark Marked gene: TWNK as ready
BabyScreen+ newborn screening v0.835 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from Spinocerebellar ataxia infantile-onset to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245
BabyScreen+ newborn screening v0.832 TYMP Zornitza Stark Marked gene: TYMP as ready
BabyScreen+ newborn screening v0.829 TYR Zornitza Stark Marked gene: TYR as ready
BabyScreen+ newborn screening v0.826 UBE2T Zornitza Stark Marked gene: UBE2T as ready
BabyScreen+ newborn screening v0.825 COL5A1 Zornitza Stark Marked gene: COL5A1 as ready
BabyScreen+ newborn screening v0.825 COL5A1 Zornitza Stark Phenotypes for gene: COL5A1 were changed from Ehlers-Danlos syndrome, type I to Ehlers-Danlos syndrome, classic type, 1, MIM# 130000; Fibromuscular dysplasia, multifocal, MIM# 619329
BabyScreen+ newborn screening v0.823 COL5A1 Zornitza Stark reviewed gene: COL5A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, classic type, 1, MIM# 130000, Fibromuscular dysplasia, multifocal, MIM# 619329; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.823 COL6A3 Zornitza Stark Marked gene: COL6A3 as ready
BabyScreen+ newborn screening v0.823 COL6A3 Zornitza Stark Phenotypes for gene: COL6A3 were changed from Ullrich congenital muscular dystrophy to Bethlem myopathy 1 MIM#158810; Dystonia 27 MIM#616411; Ullrich congenital muscular dystrophy 1 MIM#254090
BabyScreen+ newborn screening v0.820 COL6A3 Zornitza Stark reviewed gene: COL6A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bethlem myopathy 1 MIM#158810, Dystonia 27 MIM#616411, Ullrich congenital muscular dystrophy 1 MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.820 COL6A2 Zornitza Stark Marked gene: COL6A2 as ready
BabyScreen+ newborn screening v0.820 COL6A2 Zornitza Stark Phenotypes for gene: COL6A2 were changed from Ullrich congenital muscular dystrophy to Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090
BabyScreen+ newborn screening v0.817 COL6A2 Zornitza Stark reviewed gene: COL6A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bethlem myopathy 1 MIM#158810, Ullrich congenital muscular dystrophy 1 MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.817 COL6A1 Zornitza Stark Marked gene: COL6A1 as ready
BabyScreen+ newborn screening v0.817 COL6A1 Zornitza Stark Phenotypes for gene: COL6A1 were changed from Ullrich congenital muscular dystrophy to Bethlem myopathy MIM#158810; Ullrich congenital muscular dystrophy MIM#254090
BabyScreen+ newborn screening v0.814 COL6A1 Zornitza Stark reviewed gene: COL6A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bethlem myopathy MIM#158810, Ullrich congenital muscular dystrophy MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.814 COL9A3 Zornitza Stark Marked gene: COL9A3 as ready
BabyScreen+ newborn screening v0.813 TTPA Zornitza Stark Marked gene: TTPA as ready
BabyScreen+ newborn screening v0.811 TTR Zornitza Stark Marked gene: TTR as ready
BabyScreen+ newborn screening v0.811 TTR Zornitza Stark Phenotypes for gene: TTR were changed from Amyloidosis, hereditary, transthyretin-related to Amyloidosis, hereditary, transthyretin-related MIM#105210
BabyScreen+ newborn screening v0.808 PDX1 Zornitza Stark Marked gene: PDX1 as ready
BabyScreen+ newborn screening v0.807 PDE4D Zornitza Stark Marked gene: PDE4D as ready
BabyScreen+ newborn screening v0.805 PCNT Zornitza Stark Marked gene: PCNT as ready
BabyScreen+ newborn screening v0.805 PCNT Zornitza Stark Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism type 2 to Microcephalic osteodysplastic primordial dwarfism, type II, 210720
BabyScreen+ newborn screening v0.803 PCDH15 Zornitza Stark Marked gene: PCDH15 as ready
BabyScreen+ newborn screening v0.802 TTR Lilian Downie reviewed gene: TTR: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301373, PMID: 3032328, PMID: 29972753, PMID: 29972757; Phenotypes: Amyloidosis, hereditary, transthyretin-related MIM#105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.802 PCNT David Amor reviewed gene: PCNT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type II, 210720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.802 CRTAP Zornitza Stark Marked gene: CRTAP as ready
BabyScreen+ newborn screening v0.801 CSF2RA Zornitza Stark Marked gene: CSF2RA as ready
BabyScreen+ newborn screening v0.800 CSF2RA Zornitza Stark reviewed gene: CSF2RA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 4, MIM# 300770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.800 CSF3R Zornitza Stark Marked gene: CSF3R as ready
BabyScreen+ newborn screening v0.800 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from Neutropenia, severe congenital, 7, autosomal recessive , MIM#617014; Neutrophilia, hereditary , MIM# 162830 to Neutropenia, severe congenital, 7, autosomal recessive , MIM#617014
BabyScreen+ newborn screening v0.798 UBR1 Zornitza Stark Marked gene: UBR1 as ready
BabyScreen+ newborn screening v0.798 UBR1 Zornitza Stark Phenotypes for gene: UBR1 were changed from Johanson-Blizzard syndrome to Johanson-Blizzard syndrome MIM#243800
BabyScreen+ newborn screening v0.795 UGT1A1 Zornitza Stark Marked gene: UGT1A1 as ready
BabyScreen+ newborn screening v0.795 UGT1A1 Zornitza Stark Phenotypes for gene: UGT1A1 were changed from Crigler-Najjar syndrome to Crigler-Najjar syndrome, type I, MIM# 218800
BabyScreen+ newborn screening v0.793 UBR1 Lilian Downie reviewed gene: UBR1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 24599544; Phenotypes: Johanson-Blizzard syndrome MIM#243800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.793 UGT1A1 Lilian Downie reviewed gene: UGT1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26595536, PMID: 29448836; Phenotypes: Crigler-Najjar syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.793 CSTB Zornitza Stark Marked gene: CSTB as ready
BabyScreen+ newborn screening v0.791 CTC1 Zornitza Stark Marked gene: CTC1 as ready
BabyScreen+ newborn screening v0.789 CTPS1 Zornitza Stark Marked gene: CTPS1 as ready
BabyScreen+ newborn screening v0.789 CTSK Zornitza Stark Marked gene: CTSK as ready
BabyScreen+ newborn screening v0.787 CYP27A1 John Christodoulou changed review comment from: treatable with chenodeoxycholic acid and pravastatin; GeneReviews - www.ncbi.nlm.nih.gov/books/NBK1409/#ctx.Summary

Best effect if started early (PMID: 7964884); to: Onset of disease can be in infancy childhood, with a case made for newborn screening/genetic testing because of effective treatments being available - PMID: 33630770

treatable with chenodeoxycholic acid and pravastatin; GeneReviews - www.ncbi.nlm.nih.gov/books/NBK1409/#ctx.Summary

Best effect if started early (PMID: 7964884)
BabyScreen+ newborn screening v0.787 PCBD1 John Christodoulou changed review comment from: is on the current VCGS newborn screening panel; to: is on the current VCGS newborn screening panel by virtue of phenylalanine being the primary first tier metabolite that is analysed.

Hyperphenylalaninaemia when present in the newborn is transient. There doesn’t appear to be cognitive impairment if untreated, but some individuals develop diabetes and/or mild hypomagnesaemia later in adolescence. There does not appear to be any evidence that any treatments in infancy would have an effect on these two late effects. See: PMID: 32456656

So, I think we can take this one off the list.
BabyScreen+ newborn screening v0.787 CUL7 Zornitza Stark Marked gene: CUL7 as ready
BabyScreen+ newborn screening v0.785 CXCR4 Zornitza Stark Marked gene: CXCR4 as ready
BabyScreen+ newborn screening v0.785 CYBA Zornitza Stark Marked gene: CYBA as ready
BabyScreen+ newborn screening v0.785 CYBB Zornitza Stark Marked gene: CYBB as ready
BabyScreen+ newborn screening v0.785 CYP4F22 Zornitza Stark Marked gene: CYP4F22 as ready
BabyScreen+ newborn screening v0.783 MMAB Zornitza Stark Marked gene: MMAB as ready
BabyScreen+ newborn screening v0.783 IVD Zornitza Stark Marked gene: IVD as ready
BabyScreen+ newborn screening v0.783 GBA Zornitza Stark Marked gene: GBA as ready
BabyScreen+ newborn screening v0.782 G6PC3 Zornitza Stark Marked gene: G6PC3 as ready
BabyScreen+ newborn screening v0.782 CREBBP Zornitza Stark Marked gene: CREBBP as ready
BabyScreen+ newborn screening v0.780 COL1A2 Zornitza Stark Marked gene: COL1A2 as ready
BabyScreen+ newborn screening v0.779 COL1A1 Zornitza Stark Marked gene: COL1A1 as ready
BabyScreen+ newborn screening v0.778 COL17A1 Zornitza Stark Marked gene: COL17A1 as ready
BabyScreen+ newborn screening v0.776 PHYH Zornitza Stark Marked gene: PHYH as ready
BabyScreen+ newborn screening v0.774 PHKG2 Zornitza Stark Marked gene: PHKG2 as ready
BabyScreen+ newborn screening v0.773 PHKB Zornitza Stark Marked gene: PHKB as ready
BabyScreen+ newborn screening v0.772 PHKA2 Zornitza Stark Marked gene: PHKA2 as ready
BabyScreen+ newborn screening v0.770 PHGDH Zornitza Stark Marked gene: PHGDH as ready
BabyScreen+ newborn screening v0.770 PGM1 Zornitza Stark Marked gene: PGM1 as ready
BabyScreen+ newborn screening v0.770 PFKM Zornitza Stark Marked gene: PFKM as ready
BabyScreen+ newborn screening v0.767 PEX7 Zornitza Stark Marked gene: PEX7 as ready
BabyScreen+ newborn screening v0.765 PEX6 Zornitza Stark Marked gene: PEX6 as ready
BabyScreen+ newborn screening v0.763 PEX5 Zornitza Stark Marked gene: PEX5 as ready
BabyScreen+ newborn screening v0.761 PEX3 Zornitza Stark Marked gene: PEX3 as ready
BabyScreen+ newborn screening v0.759 PEX26 Zornitza Stark Marked gene: PEX26 as ready
BabyScreen+ newborn screening v0.757 PEX2 Zornitza Stark Marked gene: PEX2 as ready
BabyScreen+ newborn screening v0.755 PEX13 Zornitza Stark Marked gene: PEX13 as ready
BabyScreen+ newborn screening v0.753 PEX12 Zornitza Stark Marked gene: PEX12 as ready
BabyScreen+ newborn screening v0.751 PEX10 Zornitza Stark Marked gene: PEX10 as ready
BabyScreen+ newborn screening v0.749 PAX6 Zornitza Stark Marked gene: PAX6 as ready
BabyScreen+ newborn screening v0.747 PAX3 Zornitza Stark Marked gene: PAX3 as ready
BabyScreen+ newborn screening v0.747 PAX3 Zornitza Stark Phenotypes for gene: PAX3 were changed from Waardenburg syndrome to Waardenburg syndrome, type 1, OMIM 193500
BabyScreen+ newborn screening v0.746 PANK2 Zornitza Stark Marked gene: PANK2 as ready
BabyScreen+ newborn screening v0.744 PAK3 Zornitza Stark Marked gene: PAK3 as ready
BabyScreen+ newborn screening v0.744 PAK3 Zornitza Stark Phenotypes for gene: PAK3 were changed from Mental retardation syndrome, X-linked to Mental retardation syndrome, X-linked 30, MIM#300558
BabyScreen+ newborn screening v0.742 P2RY12 Zornitza Stark Marked gene: P2RY12 as ready
BabyScreen+ newborn screening v0.740 PEX1 Zornitza Stark Marked gene: PEX1 as ready
BabyScreen+ newborn screening v0.738 PDHX Zornitza Stark Marked gene: PDHX as ready
BabyScreen+ newborn screening v0.736 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
BabyScreen+ newborn screening v0.734 PC Zornitza Stark Marked gene: PC as ready
BabyScreen+ newborn screening v0.734 PC Zornitza Stark Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency to Pyruvate carboxylase deficiency, MIM# 266150
BabyScreen+ newborn screening v0.732 PC Zornitza Stark reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pyruvate carboxylase deficiency, MIM# 266150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.732 PAX8 Zornitza Stark Marked gene: PAX8 as ready
BabyScreen+ newborn screening v0.728 ADAR Zornitza Stark commented on gene: ADAR: To be discussed further with neurology.
BabyScreen+ newborn screening v0.727 UROD Zornitza Stark Marked gene: UROD as ready
BabyScreen+ newborn screening v0.723 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 62, MIM# 617938; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.721 SCN1A Zornitza Stark reviewed gene: SCN1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.721 PCBD1 Zornitza Stark changed review comment from: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.

For review; to: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.
BabyScreen+ newborn screening v0.719 PAX3 David Amor reviewed gene: PAX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome, type 1, OMIM 193500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.719 PALB2 David Amor reviewed gene: PALB2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group N, OMIM 610832 (AR), Breast cancer, susceptibility to (OMIM 114480) (AD); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 PHYH John Christodoulou reviewed gene: PHYH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: retinitis pigmentosa with night blindness, cataracts, polyneuropathy including sensory disturbances, cerebellar ataxia, anosmia, progressive hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 PHKG2 John Christodoulou reviewed gene: PHKG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30659246, https://www.ncbi.nlm.nih.gov/books/NBK55061/#gsd9.Summary; Phenotypes: hepatomegaly, hypotonia, growth retardation, hypoglycaemia, fasting ketosis, cirrhosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 PHKB John Christodoulou reviewed gene: PHKB: Rating: GREEN; Mode of pathogenicity: None; Publications: https://www.ncbi.nlm.nih.gov/books/NBK55061/#gsd9.Summary; Phenotypes: marked hepatomegaly, hypoglycaemia, short stature, fasting ketosis, hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 PHGDH John Christodoulou reviewed gene: PHGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: growth retardation, congenital microcephaly, hypogonadism, hypertonia, severe ID, epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 PGM1 John Christodoulou reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32681750; Phenotypes: cleft lip, bifid uvula, hepatopathy, intermittent hypoglycemia, short stature, exercise intolerance, increased serum creatine kinase, rhabdomyolysis, dilated cardiomyopathy, hypogonadotropic hypogonadism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 MLYCD John Christodoulou reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28781843, PMID: 20549361; Phenotypes: hypoglycaemia, metabolic acidosis, cardiomyopathy, ID, seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 MAN2B1 John Christodoulou reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31222755, PMID: 31241255; Phenotypes: ID, coarse facial features, deafness, dysostosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.719 SLC17A5 Seb Lunke Marked gene: SLC17A5 as ready
BabyScreen+ newborn screening v0.717 SLC16A2 Seb Lunke Marked gene: SLC16A2 as ready
BabyScreen+ newborn screening v0.715 SLC12A6 Seb Lunke Marked gene: SLC12A6 as ready
BabyScreen+ newborn screening v0.713 SLC12A3 Seb Lunke Marked gene: SLC12A3 as ready
BabyScreen+ newborn screening v0.711 SLC12A1 Seb Lunke Marked gene: SLC12A1 as ready
BabyScreen+ newborn screening v0.711 SLC12A1 Seb Lunke Phenotypes for gene: SLC12A1 were changed from Bartter syndrome to Bartter syndrome, type 1, MIM# 601678
BabyScreen+ newborn screening v0.710 SLC12A1 Seb Lunke reviewed gene: SLC12A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 1, MIM# 601678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.710 SKI Seb Lunke Marked gene: SKI as ready
BabyScreen+ newborn screening v0.708 SIX3 Seb Lunke Marked gene: SIX3 as ready
BabyScreen+ newborn screening v0.706 SIX1 Seb Lunke Marked gene: SIX1 as ready
BabyScreen+ newborn screening v0.704 SIL1 Seb Lunke Marked gene: SIL1 as ready
BabyScreen+ newborn screening v0.704 SIL1 Seb Lunke Phenotypes for gene: SIL1 were changed from Marinesco-Sjogren syndrome to Marinesco-Sjogren syndrome, MIM#248800
BabyScreen+ newborn screening v0.702 SIL1 Seb Lunke reviewed gene: SIL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Marinesco-Sjogren syndrome, MIM#248800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.702 SI Seb Lunke Marked gene: SI as ready
BabyScreen+ newborn screening v0.702 SHH Seb Lunke Marked gene: SHH as ready
BabyScreen+ newborn screening v0.700 SHANK3 Seb Lunke Marked gene: SHANK3 as ready
BabyScreen+ newborn screening v0.699 SH3TC2 Seb Lunke Marked gene: SH3TC2 as ready
BabyScreen+ newborn screening v0.699 SH3TC2 Seb Lunke Phenotypes for gene: SH3TC2 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 4C MIM#601596
BabyScreen+ newborn screening v0.697 SH3TC2 Seb Lunke reviewed gene: SH3TC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4C MIM#601596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.697 SH2D1A Seb Lunke Marked gene: SH2D1A as ready
BabyScreen+ newborn screening v0.695 SGSH Seb Lunke Marked gene: SGSH as ready
BabyScreen+ newborn screening v0.695 SGSH Seb Lunke Phenotypes for gene: SGSH were changed from Mucopolysaccharidisis type IIIA (Sanfilippo A) to Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900
BabyScreen+ newborn screening v0.693 SGSH Seb Lunke reviewed gene: SGSH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.693 SGCB Seb Lunke Marked gene: SGCB as ready
BabyScreen+ newborn screening v0.693 SGCG Seb Lunke Marked gene: SGCG as ready
BabyScreen+ newborn screening v0.693 SGCB Seb Lunke Phenotypes for gene: SGCB were changed from Muscular dystrophy, limb-girdle, type 2E to Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286
BabyScreen+ newborn screening v0.692 SGCD Seb Lunke Marked gene: SGCD as ready
BabyScreen+ newborn screening v0.692 SGCG Seb Lunke Phenotypes for gene: SGCG were changed from Muscular dystrophy, limb-girdle, type 2C to Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700
BabyScreen+ newborn screening v0.688 SGCG Seb Lunke reviewed gene: SGCG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.688 SGCD Seb Lunke reviewed gene: SGCD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.688 SGCB Seb Lunke reviewed gene: SGCB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.688 SGCA Seb Lunke Marked gene: SGCA as ready
BabyScreen+ newborn screening v0.688 SGCA Seb Lunke Phenotypes for gene: SGCA were changed from Muscular dystrophy, limb-girdle, type 2D to Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099
BabyScreen+ newborn screening v0.686 SGCA Seb Lunke reviewed gene: SGCA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.686 COL13A1 Zornitza Stark Marked gene: COL13A1 as ready
BabyScreen+ newborn screening v0.685 COL11A2 Zornitza Stark Marked gene: COL11A2 as ready
BabyScreen+ newborn screening v0.682 COL11A1 Zornitza Stark Marked gene: COL11A1 as ready
BabyScreen+ newborn screening v0.681 COG5 Zornitza Stark Marked gene: COG5 as ready
BabyScreen+ newborn screening v0.679 OXCT1 Zornitza Stark Marked gene: OXCT1 as ready
BabyScreen+ newborn screening v0.679 OTOGL Zornitza Stark Marked gene: OTOGL as ready
BabyScreen+ newborn screening v0.678 OTOF Zornitza Stark Marked gene: OTOF as ready
BabyScreen+ newborn screening v0.677 OTOA Zornitza Stark Marked gene: OTOA as ready
BabyScreen+ newborn screening v0.676 OTC Zornitza Stark Marked gene: OTC as ready
BabyScreen+ newborn screening v0.676 OSTM1 Zornitza Stark Marked gene: OSTM1 as ready
BabyScreen+ newborn screening v0.673 DPAGT1 Zornitza Stark changed review comment from: Bi-allelic variants cause either multi-system CDG or congenital myasthenia graves.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

Phenotype may already be apparent in newborn period so clinical correlation possible.; to: Bi-allelic variants cause either multi-system CDG or congenital myasthenia gravis.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

Phenotype may already be apparent in newborn period so clinical correlation possible.
BabyScreen+ newborn screening v0.673 UMOD Zornitza Stark Marked gene: UMOD as ready
BabyScreen+ newborn screening v0.670 OTOA David Amor changed review comment from: Gene-disease association: strong. Note that large deletions are relatively common - will we detect by WGS?

Severity: moderate to severe prelingual sensorineural recessive deafness

Age of onset: congenital

Non-molecular confirmatory testing: audiology

Treatment: symptomatic only therefore exclude; to: Gene-disease association: strong. Note that large deletions are relatively common - will we detect by WGS?

Severity: moderate to severe prelingual sensorineural recessive deafness

Age of onset: congenital

Non-molecular confirmatory testing: audiology

Treatment: HA, CI.
BabyScreen+ newborn screening v0.670 OTC David Amor reviewed gene: OTC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 311250 Ornithine transcarbamylase deficiency; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.670 UNC13D Zornitza Stark Marked gene: UNC13D as ready
BabyScreen+ newborn screening v0.669 SFTPC Zornitza Stark reviewed gene: SFTPC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 2, MIM# 610913; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.667 MEN1 Zornitza Stark changed review comment from: For review re age of onset; to: For review re age of onset: surveillance starts age 5, disease onset generally later.
BabyScreen+ newborn screening v0.667 MEFV Zornitza Stark changed review comment from: Generally bi-allelic disease. There are a small number of variants linked to mono-allelic disease. Are they worth including specifically?

For review.; to: Generally bi-allelic disease. There are a small number of variants linked to mono-allelic disease. Are they worth including specifically?

Reviewed: only include bi-allelic disease.
BabyScreen+ newborn screening v0.667 MAGI2 Zornitza Stark Marked gene: MAGI2 as ready
BabyScreen+ newborn screening v0.664 LRP5 Zornitza Stark changed review comment from: Gene is associated with multiple phenotypes.

Bisphosphanate is used to treat osteoporosis. Onset of bone fragility is in childhood.

Non-genetic confirmatory testing: skeletal survey, but uncertain at what stage abnormalities would appear.

For review.; to: Gene is associated with multiple phenotypes.

Bisphosphanate is used to treat osteoporosis. Onset of bone fragility is in childhood.

Non-genetic confirmatory testing: skeletal survey, but uncertain at what stage abnormalities would appear.

For review: only include bi-allelic disease.
BabyScreen+ newborn screening v0.664 FUCA1 Zornitza Stark changed review comment from: Non-genetic confirmatory testing: fucosidase activity in serum or plasma

For review regarding utility of BMT.; to: Non-genetic confirmatory testing: fucosidase activity in serum or plasma

For review regarding utility of BMT: include, uncertain if pre-symptomatic BMT may have better outcomes than currently reported.
BabyScreen+ newborn screening v0.664 ETFB Zornitza Stark changed review comment from: Well established gene-disease association.

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress.

Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates

Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis; to: Well established gene-disease association.

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress.

Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates

Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis

Predominantly neonatal onset.
BabyScreen+ newborn screening v0.662 LDLR Zornitza Stark changed review comment from: ClinGen: 'strong actionability' in paediatric patients.

For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.; to: ClinGen: 'strong actionability' in paediatric patients.

For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.

Include bi-allelic disease in gNBS. Continue considering if and when mono-allelic disease should be included.
BabyScreen+ newborn screening v0.662 GATA4 Zornitza Stark Marked gene: GATA4 as ready
BabyScreen+ newborn screening v0.662 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from Congenital heart defects to Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429
BabyScreen+ newborn screening v0.661 FLAD1 Zornitza Stark changed review comment from: Well established gene-disease association, more than 10 families reported.

The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment.

For discussion. Included as a treatable disorder in rx-genes.

Confirmatory non-genetic testing: Plasma acylcarnitine profile, Urine organic acid analysis,; to: Well established gene-disease association, more than 10 families reported.

The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment.

Included as a treatable disorder in rx-genes.

Confirmatory non-genetic testing: Plasma acylcarnitine profile, Urine organic acid analysis,
BabyScreen+ newborn screening v0.661 DPAGT1 Zornitza Stark changed review comment from: Bi-allelic variants cause either multi-system CDG or congenital myasthenia graves.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

For review.; to: Bi-allelic variants cause either multi-system CDG or congenital myasthenia graves.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

Phenotype may already be apparent in newborn period so clinical correlation possible.
BabyScreen+ newborn screening v0.660 COQ8B Zornitza Stark changed review comment from: Well established gene-disease association.

Disease onset typically between ages 10 and 20 years, although several had earlier onset, including 1 patient with onset in the first year of life.

Treatment: CoQ10 supplementation, improves nephrotic features

For review: re age of onset; to: Well established gene-disease association.

Disease onset typically between ages 10 and 20 years, although several had earlier onset, including 1 patient with onset in the first year of life.

Treatment: CoQ10 supplementation, improves nephrotic features

For review: re age of onset -- predominantly later onset, so not included
BabyScreen+ newborn screening v0.660 COCH Zornitza Stark Marked gene: COCH as ready
BabyScreen+ newborn screening v0.658 CNGB3 Zornitza Stark Marked gene: CNGB3 as ready
BabyScreen+ newborn screening v0.656 CLRN1 Zornitza Stark Marked gene: CLRN1 as ready
BabyScreen+ newborn screening v0.654 CLPP Zornitza Stark Marked gene: CLPP as ready
BabyScreen+ newborn screening v0.654 CLDN19 Zornitza Stark Marked gene: CLDN19 as ready
BabyScreen+ newborn screening v0.654 CLDN19 Zornitza Stark Phenotypes for gene: CLDN19 were changed from Hypomagnesemia 5, renal, with ocular involvement to Deafness, autosomal recessive 116 MIM#619093
BabyScreen+ newborn screening v0.652 CLDN14 Zornitza Stark Marked gene: CLDN14 as ready
BabyScreen+ newborn screening v0.652 CLDN14 Zornitza Stark Phenotypes for gene: CLDN14 were changed from Hearing loss, non-syndromic, autosomal recessive to Deafness, autosomal recessive 29, MIM# 614035
BabyScreen+ newborn screening v0.651 SFTPC Seb Lunke Marked gene: SFTPC as ready
BabyScreen+ newborn screening v0.651 SFTPC Seb Lunke Phenotypes for gene: SFTPC were changed from Interstitial lung disease; Surfactant metabolism dysfunction, pulmonary, 2 MIM# 178620 to Surfactant metabolism dysfunction, pulmonary, 2, MIM# 610913
BabyScreen+ newborn screening v0.650 SFTPC Seb Lunke reviewed gene: SFTPC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 2, MIM# 610913; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.650 CLCN7 Zornitza Stark Marked gene: CLCN7 as ready
BabyScreen+ newborn screening v0.650 CEP78 Zornitza Stark Marked gene: CEP78 as ready
BabyScreen+ newborn screening v0.650 CEP78 Zornitza Stark Phenotypes for gene: CEP78 were changed from Cone-rod dystrophy and hearing loss to Cone-rod dystrophy and hearing loss MIM#617236
BabyScreen+ newborn screening v0.648 CEP78 Zornitza Stark changed review comment from: Gene-disease association assessed as 'strong' by ClinGen.

Atypical Usher phenotype.

However, onset of visual and hearing symptoms is variable, ranging from first to fourth decade, exclude for this reason.; to: Gene-disease association assessed as 'strong' by ClinGen.

Atypical Usher phenotype.

However, onset of visual and hearing symptoms is variable, ranging from first to fourth decade, exclude for this reason, unlikely to be detected by the newborn hearing screening program.
BabyScreen+ newborn screening v0.648 CEP78 Zornitza Stark reviewed gene: CEP78: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy and hearing loss MIM#617236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.648 SFTPB Seb Lunke Marked gene: SFTPB as ready
BabyScreen+ newborn screening v0.648 SFTPB Seb Lunke Phenotypes for gene: SFTPB were changed from Surfactant metabolism dysfunction, pulmonary to Surfactant metabolism dysfunction, pulmonary, 1, MIM# 265120
BabyScreen+ newborn screening v0.646 SFTPB Seb Lunke reviewed gene: SFTPB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 1, MIM# 265120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.646 SETX Seb Lunke Marked gene: SETX as ready
BabyScreen+ newborn screening v0.646 SETX Seb Lunke Phenotypes for gene: SETX were changed from Ataxia-ocular apraxia 2 to Spinocerebellar ataxia, autosomal recessive 1, 606002
BabyScreen+ newborn screening v0.644 SETX Seb Lunke reviewed gene: SETX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia, autosomal recessive 1, 606002; Mode of inheritance: None
BabyScreen+ newborn screening v0.644 SETBP1 Seb Lunke Marked gene: SETBP1 as ready
BabyScreen+ newborn screening v0.642 CLCN5 Zornitza Stark Marked gene: CLCN5 as ready
BabyScreen+ newborn screening v0.640 CIB2 Zornitza Stark Marked gene: CIB2 as ready
BabyScreen+ newborn screening v0.640 CHM Zornitza Stark Marked gene: CHM as ready
BabyScreen+ newborn screening v0.638 CHKB Zornitza Stark Marked gene: CHKB as ready
BabyScreen+ newborn screening v0.638 CHKB Zornitza Stark Phenotypes for gene: CHKB were changed from Muscular dystrophy, congenital, megaconial type to Muscular dystrophy, congenital, megaconial type, MIM# 602541
BabyScreen+ newborn screening v0.636 CHKB Zornitza Stark reviewed gene: CHKB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, congenital, megaconial type, MIM# 602541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.636 CHD2 Zornitza Stark Marked gene: CHD2 as ready
BabyScreen+ newborn screening v0.634 CFP Zornitza Stark Marked gene: CFP as ready
BabyScreen+ newborn screening v0.634 CFL2 Zornitza Stark Marked gene: CFL2 as ready
BabyScreen+ newborn screening v0.632 SERPINA1 Seb Lunke Marked gene: SERPINA1 as ready
BabyScreen+ newborn screening v0.630 CFC1 Zornitza Stark Marked gene: CFC1 as ready
BabyScreen+ newborn screening v0.630 CFC1 Zornitza Stark Phenotypes for gene: CFC1 were changed from Congenital heart defects to Heterotaxy, visceral, 2, autosomal MIM#605376
BabyScreen+ newborn screening v0.628 CEP83 Zornitza Stark Marked gene: CEP83 as ready
BabyScreen+ newborn screening v0.627 CEP290 Zornitza Stark Marked gene: CEP290 as ready
BabyScreen+ newborn screening v0.627 CEP290 Zornitza Stark Phenotypes for gene: CEP290 were changed from Joubert syndrome to Bardet-Biedl syndrome 14, MIM# 615991; Joubert syndrome 5 610188; Leber congenital amaurosis 10, MIM# 611755; Meckel syndrome 4, MIM# 611134; Senior-Loken syndrome 6, MIM# 610189
BabyScreen+ newborn screening v0.625 CEP290 Zornitza Stark reviewed gene: CEP290: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 14, MIM# 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, MIM# 611755, Meckel syndrome 4, MIM# 611134, Senior-Loken syndrome 6, MIM# 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.625 SELENON Seb Lunke Marked gene: SELENON as ready
BabyScreen+ newborn screening v0.625 SELENON Seb Lunke Phenotypes for gene: SELENON were changed from Muscular dystrophy, rigid spine; Myopathy, congenital, with fiber-type disproportion to Myopathy, congenital, with fiber-type disproportion, MIM# 255310
BabyScreen+ newborn screening v0.622 VCP Zornitza Stark Marked gene: VCP as ready
BabyScreen+ newborn screening v0.622 VCP Zornitza Stark Phenotypes for gene: VCP were changed from Inclusion body myopathy with early-onset paget disease and frontotemporal dementia to Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia MIM#167320; Charcot-Marie-Tooth disease, type 2Y, MIM# 616687
BabyScreen+ newborn screening v0.619 VCP Zornitza Stark reviewed gene: VCP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 2Y, MIM# 616687; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.619 VDR Zornitza Stark Marked gene: VDR as ready
BabyScreen+ newborn screening v0.617 VHL Zornitza Stark Marked gene: VHL as ready
BabyScreen+ newborn screening v0.615 CEP152 Zornitza Stark Marked gene: CEP152 as ready
BabyScreen+ newborn screening v0.615 CEP152 Zornitza Stark Phenotypes for gene: CEP152 were changed from Seckel syndrome to Microcephaly 9, primary, autosomal recessive, MIM# 614852; Seckel syndrome 5, MIM# 613823
BabyScreen+ newborn screening v0.613 CEP152 Zornitza Stark reviewed gene: CEP152: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 9, primary, autosomal recessive, MIM# 614852, Seckel syndrome 5, MIM# 613823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.613 CDT1 Zornitza Stark Marked gene: CDT1 as ready
BabyScreen+ newborn screening v0.612 CDSN Zornitza Stark Marked gene: CDSN as ready
BabyScreen+ newborn screening v0.609 CDKL5 Zornitza Stark Marked gene: CDKL5 as ready
BabyScreen+ newborn screening v0.609 CDKL5 Zornitza Stark Phenotypes for gene: CDKL5 were changed from Epileptic encephalopathy, early infantile, 2 to Epileptic encephalopathy, early infantile, 2, MIM 300672
BabyScreen+ newborn screening v0.607 CDKL5 Zornitza Stark reviewed gene: CDKL5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 2, MIM 300672; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.607 CDH23 Zornitza Stark Marked gene: CDH23 as ready
BabyScreen+ newborn screening v0.606 CDC14A Zornitza Stark Marked gene: CDC14A as ready
BabyScreen+ newborn screening v0.606 GATA4 Alison Yeung changed review comment from: Well-established gene-disease association for congenital heart defects and neonatal diabetes
Onset: infancy but variable expressivity and incomplete penetrance common for cardiac defects
Severity: variable defects. No syndromic features, no association with arrhythmias
Treatment: Echocardiogram and surgical repair for cardiac defects; Insulin for neonatal diabetes; to: Well-established gene-disease association for congenital heart defects and neonatal diabetes
Onset: infancy but variable expressivity and incomplete penetrance common for cardiac defects
Severity: variable defects. No syndromic features, no association with arrhythmias
Treatment: Echocardiogram and surgical repair for cardiac defects; Insulin for neonatal diabetes
BabyScreen+ newborn screening v0.606 GATA4 Alison Yeung changed review comment from: Well-established gene-disease association
Onset: infancy (congenital heart defects) but variable expressivity and incomplete penetrance common
Severity: variable defects. No syndromic features, no association with arrhythmias
Treatment: Echocardiogram and surgical repair; to: Well-established gene-disease association for congenital heart defects and neonatal diabetes
Onset: infancy but variable expressivity and incomplete penetrance common for cardiac defects
Severity: variable defects. No syndromic features, no association with arrhythmias
Treatment: Echocardiogram and surgical repair for cardiac defects; Insulin for neonatal diabetes
BabyScreen+ newborn screening v0.606 GATA4 Alison Yeung reviewed gene: GATA4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial septal defect 2 MIM#607941, Atrioventricular septal defect 4 MIM#614430, Ventricular septal defect 1 MIM#614429; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.606 DDR2 Zornitza Stark Marked gene: DDR2 as ready
BabyScreen+ newborn screening v0.606 DDR2 Zornitza Stark Phenotypes for gene: DDR2 were changed from Spondylometaepiphyseal dysplasia, short limb-hand type to Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665; Warburg-Cinotti syndrome, MIM# 618175
BabyScreen+ newborn screening v0.604 DDR2 Zornitza Stark edited their review of gene: DDR2: Added comment: AR LoF variants cause a skeletal dysplasia of perinatal onset, whereas AD GoF variants cause a syndromic disorder.

No specific treatment for either.; Changed phenotypes: Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665, Warburg-Cinotti syndrome, MIM# 618175
BabyScreen+ newborn screening v0.604 VCP Lilian Downie reviewed gene: VCP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 16247064, PMID: 21145000; Phenotypes: Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia MIM#167320; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.604 CD79B Zornitza Stark Marked gene: CD79B as ready
BabyScreen+ newborn screening v0.603 CD79A Zornitza Stark Marked gene: CD79A as ready
BabyScreen+ newborn screening v0.603 CD40LG Zornitza Stark Marked gene: CD40LG as ready
BabyScreen+ newborn screening v0.602 CD3E Zornitza Stark Marked gene: CD3E as ready
BabyScreen+ newborn screening v0.602 CD3D Zornitza Stark Marked gene: CD3D as ready
BabyScreen+ newborn screening v0.602 VIPAS39 Zornitza Stark Marked gene: VIPAS39 as ready
BabyScreen+ newborn screening v0.602 VIPAS39 Zornitza Stark Phenotypes for gene: VIPAS39 were changed from Arthrogryposis, renal dysfunction and cholestasis to Arthrogryposis, renal dysfunction, and cholestasis MIM#613404
BabyScreen+ newborn screening v0.599 VIPAS39 Zornitza Stark reviewed gene: VIPAS39: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis MIM#613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.599 VLDLR Zornitza Stark Marked gene: VLDLR as ready
BabyScreen+ newborn screening v0.599 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion MIM#224050
BabyScreen+ newborn screening v0.597 VPS13A Zornitza Stark Marked gene: VPS13A as ready
BabyScreen+ newborn screening v0.595 VPS13B Zornitza Stark Marked gene: VPS13B as ready
BabyScreen+ newborn screening v0.593 ARSA Zornitza Stark Publications for gene: ARSA were set to
BabyScreen+ newborn screening v0.592 ARSA Zornitza Stark Tag for review was removed from gene: ARSA.
BabyScreen+ newborn screening v0.592 GCK Zornitza Stark Marked gene: GCK as ready
BabyScreen+ newborn screening v0.591 GCK Zornitza Stark reviewed gene: GCK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853), Diabetes mellitus, permanent neonatal 1, AR (MIM#606176), Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485), MODY, type II, AD (MIM#125851); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.591 G6PC Zornitza Stark Marked gene: G6PC as ready
BabyScreen+ newborn screening v0.590 FUCA1 Zornitza Stark Marked gene: FUCA1 as ready
BabyScreen+ newborn screening v0.588 VIPAS39 Lilian Downie reviewed gene: VIPAS39: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35761207; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis MIM#613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.588 VLDLR Lilian Downie reviewed gene: VLDLR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion MIM#224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.588 ARSA John Christodoulou reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25987178, PMID: 23348427, PMID: 33195324; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.587 CYP11A1 Zornitza Stark Marked gene: CYP11A1 as ready
BabyScreen+ newborn screening v0.587 CYP11A1 Zornitza Stark changed review comment from: Well established gene-disease association. Congenital onset.

For review: should we include mono-allelic variants?; to: Well established gene-disease association. Congenital onset.

Mono-allelic variants discussed: a single family reported only. Does not meet criteria for inclusion. MOI set to bi-allelic.
BabyScreen+ newborn screening v0.586 COQ7 Zornitza Stark changed review comment from: Four families reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: Four families reported only.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations. However this advice applies to the whole group of related conditions, and data on this particular condition in terms of natural history and response to treatment is currently limited.
BabyScreen+ newborn screening v0.585 CBS Zornitza Stark changed review comment from: Well established gene-disease association.

Multi-system disorder, onset in infancy.
In general, individuals appear normal at birth but have a progressive disease course if untreated. Clinical features typically manifest in the first or second decade of life. Intellectual disability may be the first recognizable sign and may present as developmental delay after the first to second year of life. Myopia typically occurs after age one with the majority of untreated individuals developing ectopia lentis by age 8. Roughly half of patients show signs of osteoporosis by their teens. Cerebrovascular events typically manifest during young adulthood, though they have been reported earlier. Thromboembolism is the major cause of early death and morbidity. Among B₆-responsive individuals, a vascular event in adolescence or adulthood is often the presenting feature.

Treatment: vitamin B6 (pyridoxine), methionine-restricted diet, folate, vitamin B12, betaine. Management guidelines PMID 27778219.

Non-genetic confirmatory testing: plasma total homocysteine and plasma amino acids

Paediatric actionable gene by ClinGen.

Note excluded from reproductive carrier screening tests due to poor mappability, for review.; to: Well established gene-disease association.

Multi-system disorder, onset in infancy.
In general, individuals appear normal at birth but have a progressive disease course if untreated. Clinical features typically manifest in the first or second decade of life. Intellectual disability may be the first recognizable sign and may present as developmental delay after the first to second year of life. Myopia typically occurs after age one with the majority of untreated individuals developing ectopia lentis by age 8. Roughly half of patients show signs of osteoporosis by their teens. Cerebrovascular events typically manifest during young adulthood, though they have been reported earlier. Thromboembolism is the major cause of early death and morbidity. Among B₆-responsive individuals, a vascular event in adolescence or adulthood is often the presenting feature.

Treatment: vitamin B6 (pyridoxine), methionine-restricted diet, folate, vitamin B12, betaine. Management guidelines PMID 27778219.

Non-genetic confirmatory testing: plasma total homocysteine and plasma amino acids

Paediatric actionable gene by ClinGen.

Note excluded from reproductive carrier screening tests due to poor mappability: downgraded to Amber for now.
BabyScreen+ newborn screening v0.585 BCHE Zornitza Stark Marked gene: BCHE as ready
BabyScreen+ newborn screening v0.585 BCHE Zornitza Stark Tag for review was removed from gene: BCHE.
Tag pharmacogenomic tag was added to gene: BCHE.
BabyScreen+ newborn screening v0.585 BCHE Zornitza Stark changed review comment from: Well established gene-disease association.

Individuals are asymptomatic unless exposed to triggering agents.

Consider as a separate pharmacogenomic offering?

For review.; to: Well established gene-disease association.

Individuals are asymptomatic unless exposed to triggering agents.

Consider as a separate pharmacogenomic offering?

Group review: preventative intervention available by placing alerts in medical records.
BabyScreen+ newborn screening v0.585 ABCC6 Zornitza Stark changed review comment from: Well established gene-disease association.

Severe disorder with onset in infancy, can be fatal.

Treatment available: etidronate.

However, note excluded by other screening programs as severity difficult to predict from genotype and gene is also associated with PXE, a milder disorder.

There are also technical concerns due to 2x pseudogenes which cause mapping/variant calling issues in exons 1-9.; to: Well established gene-disease association.

Severe disorder with onset in infancy, can be fatal.

Treatment available: etidronate.

However, note excluded by other screening programs as severity difficult to predict from genotype and gene is also associated with PXE, a milder disorder. However, imaging may be able to determine severity.

There are also technical concerns due to 2x pseudogenes which cause mapping/variant calling issues in exons 1-9.
BabyScreen+ newborn screening v0.585 CDK5RAP2 Zornitza Stark Marked gene: CDK5RAP2 as ready
BabyScreen+ newborn screening v0.584 CDK5RAP2 Zornitza Stark reviewed gene: CDK5RAP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 3, primary, autosomal recessive, MIM# 604804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.584 FLAD1 Zornitza Stark Marked gene: FLAD1 as ready
BabyScreen+ newborn screening v0.583 FUCA1 John Christodoulou reviewed gene: FUCA1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33266441; Phenotypes: neurodegneration, coarse facial features, grow retardation, dysostosis multiplex, angiokeratomata, recurrent URTIs; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.583 FLAD1 John Christodoulou reviewed gene: FLAD1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30680745; Phenotypes: lactic acidosis, respiratory insufficiency, cardiomyopathy, skeletal myopathy, hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.583 CCDC40 Zornitza Stark Marked gene: CCDC40 as ready
BabyScreen+ newborn screening v0.583 CCDC40 Zornitza Stark Phenotypes for gene: CCDC40 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 15, MIM#613808
BabyScreen+ newborn screening v0.581 CCDC40 Zornitza Stark reviewed gene: CCDC40: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 15, MIM#613808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.581 CCDC39 Zornitza Stark Marked gene: CCDC39 as ready
BabyScreen+ newborn screening v0.581 CCDC39 Zornitza Stark Phenotypes for gene: CCDC39 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 14, MIM# 613807
BabyScreen+ newborn screening v0.579 CCDC39 Zornitza Stark reviewed gene: CCDC39: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 14, MIM# 613807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.579 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
BabyScreen+ newborn screening v0.577 CAVIN1 Zornitza Stark Marked gene: CAVIN1 as ready
BabyScreen+ newborn screening v0.575 CAV3 Zornitza Stark Marked gene: CAV3 as ready
BabyScreen+ newborn screening v0.575 CAV3 Zornitza Stark Phenotypes for gene: CAV3 were changed from Caveolinopathy; Muscular dystrophy, limb-girdle, type IC to Myopathy, distal, Tateyama type MIM#614321; Rippling muscle disease 2 MIM#606072; Creatine phosphokinase, elevated serum MIM#123320
BabyScreen+ newborn screening v0.573 CBL Zornitza Stark Marked gene: CBL as ready
BabyScreen+ newborn screening v0.571 CASQ2 Zornitza Stark Marked gene: CASQ2 as ready
BabyScreen+ newborn screening v0.571 CASQ2 Zornitza Stark Phenotypes for gene: CASQ2 were changed from Ventricular tachycardia, catecholaminergic polymorphic to Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
BabyScreen+ newborn screening v0.568 CASQ2 Zornitza Stark reviewed gene: CASQ2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.568 CASK Zornitza Stark Marked gene: CASK as ready
BabyScreen+ newborn screening v0.568 CASK Zornitza Stark Phenotypes for gene: CASK were changed from Mental retardation and microcephaly with pontine and cerebellar hypoplasia to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422
BabyScreen+ newborn screening v0.565 CASK Zornitza Stark reviewed gene: CASK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: FG syndrome 4 MIM#300422, Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749, Mental retardation, with or without nystagmus MIM#300422; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.565 CARD11 Zornitza Stark Marked gene: CARD11 as ready
BabyScreen+ newborn screening v0.565 CARD11 Zornitza Stark Gene: card11 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.565 CARD11 Zornitza Stark Phenotypes for gene: CARD11 were changed from Immunodeficiency 11A, MIM# 615206 to Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638
BabyScreen+ newborn screening v0.564 CARD11 Zornitza Stark reviewed gene: CARD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561803, 12818158, 23374270, 28628108; Phenotypes: Immunodeficiency 11A, autosomal recessive, MIM# 615206, Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.564 CHD7 Zornitza Stark Marked gene: CHD7 as ready
BabyScreen+ newborn screening v0.564 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from CHARGE syndrome to CHARGE syndrome, MIM# 214800
BabyScreen+ newborn screening v0.562 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome, MIM# 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.562 CA2 Zornitza Stark Marked gene: CA2 as ready
BabyScreen+ newborn screening v0.562 CA2 Zornitza Stark Phenotypes for gene: CA2 were changed from Osteopetrosis, autosomal recessive 3, with renal tubular acidosis to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730
BabyScreen+ newborn screening v0.561 CA2 Zornitza Stark reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.561 CAPN3 Zornitza Stark Marked gene: CAPN3 as ready
BabyScreen+ newborn screening v0.561 CAPN3 Zornitza Stark Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, type 2A to Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600
BabyScreen+ newborn screening v0.559 CAPN3 Zornitza Stark reviewed gene: CAPN3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.559 CACNA1F Zornitza Stark Marked gene: CACNA1F as ready
BabyScreen+ newborn screening v0.559 CACNA1F Zornitza Stark Phenotypes for gene: CACNA1F were changed from Night blindness, congenital stationary (complete), 1A, X-linked to Aland Island eye disease MIM#300600; Cone-rod dystrophy, X-linked, 3 MIM#300476; Night blindness, congenital stationary (incomplete), 2A, X-linked MIM#300071
BabyScreen+ newborn screening v0.557 CACNA1F Zornitza Stark reviewed gene: CACNA1F: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aland Island eye disease MIM#300600, Cone-rod dystrophy, X-linked, 3 MIM#300476, Night blindness, congenital stationary (incomplete), 2A, X-linked MIM#300071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.557 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
BabyScreen+ newborn screening v0.555 CABP2 Zornitza Stark Marked gene: CABP2 as ready
BabyScreen+ newborn screening v0.555 SDHD Zornitza Stark Phenotypes for gene: SDHD were changed from Mitochondrial complex II deficiency, nuclear type 3, MIM# 619167 to Mitochondrial complex II deficiency, nuclear type 3, MIM# 619167; Paragangliomas 1, with or without deafness, MIM# 168000
BabyScreen+ newborn screening v0.553 SDHD Zornitza Stark reviewed gene: SDHD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Paragangliomas 1, with or without deafness, MIM# 168000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.553 GATA3 Zornitza Stark Marked gene: GATA3 as ready
BabyScreen+ newborn screening v0.553 GATA3 Zornitza Stark reviewed gene: GATA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.553 GATA2 Zornitza Stark Marked gene: GATA2 as ready
BabyScreen+ newborn screening v0.552 GAN Zornitza Stark Marked gene: GAN as ready
BabyScreen+ newborn screening v0.550 GAMT Zornitza Stark Marked gene: GAMT as ready
BabyScreen+ newborn screening v0.550 GALNS Zornitza Stark Marked gene: GALNS as ready
BabyScreen+ newborn screening v0.550 GALNS Zornitza Stark Phenotypes for gene: GALNS were changed from Mucopolysaccharidosis IVA to Mucopolysaccharidosis IVA, MIM#253000
BabyScreen+ newborn screening v0.549 GALC Zornitza Stark Marked gene: GALC as ready
BabyScreen+ newborn screening v0.548 SDHD Seb Lunke Marked gene: SDHD as ready
BabyScreen+ newborn screening v0.548 SDHD Seb Lunke Phenotypes for gene: SDHD were changed from Hereditary Paraganglioma-Pheochromocytoma Syndromes to Mitochondrial complex II deficiency, nuclear type 3, MIM# 619167
BabyScreen+ newborn screening v0.545 SDHD Seb Lunke reviewed gene: SDHD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex II deficiency, nuclear type 3, MIM# 619167; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.545 C9 Zornitza Stark Marked gene: C9 as ready
BabyScreen+ newborn screening v0.545 C8B Zornitza Stark Marked gene: C8B as ready
BabyScreen+ newborn screening v0.545 C8A Zornitza Stark Marked gene: C8A as ready
BabyScreen+ newborn screening v0.544 C7 Zornitza Stark Marked gene: C7 as ready
BabyScreen+ newborn screening v0.544 SCO2 Seb Lunke Marked gene: SCO2 as ready
BabyScreen+ newborn screening v0.544 SCO2 Seb Lunke Phenotypes for gene: SCO2 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency to Mitochondrial complex IV deficiency, nuclear type 2, MC4DN2, MIM#604377
BabyScreen+ newborn screening v0.542 SCO2 Seb Lunke reviewed gene: SCO2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 2, MC4DN2, MIM#604377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.542 SCNN1B Seb Lunke Marked gene: SCNN1B as ready
BabyScreen+ newborn screening v0.542 SCNN1B Seb Lunke reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I, MIM# 264350 AR, MIM#0009917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.542 SCNN1A Seb Lunke Marked gene: SCNN1A as ready
BabyScreen+ newborn screening v0.541 SCNN1A Seb Lunke reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I, MIM# 264350 AR, MIM#0009917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.541 SCN8A Seb Lunke Marked gene: SCN8A as ready
BabyScreen+ newborn screening v0.541 GATA3 Alison Yeung reviewed gene: GATA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.541 GALNS Alison Yeung reviewed gene: GALNS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis IVA, MIM#253000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.541 C6 Zornitza Stark Marked gene: C6 as ready
BabyScreen+ newborn screening v0.541 FH Zornitza Stark Marked gene: FH as ready
BabyScreen+ newborn screening v0.541 FH Zornitza Stark reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fumarase deficiency, MIM#606812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.541 FBP1 Zornitza Stark Marked gene: FBP1 as ready
BabyScreen+ newborn screening v0.541 FAH Zornitza Stark Marked gene: FAH as ready
BabyScreen+ newborn screening v0.541 ETHE1 Zornitza Stark Marked gene: ETHE1 as ready
BabyScreen+ newborn screening v0.541 ETHE1 John Christodoulou reviewed gene: ETHE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: petechiae, acrocyanosis, chronic diarrhoea, ID, regression; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.541 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
BabyScreen+ newborn screening v0.541 DPAGT1 Zornitza Stark Phenotypes for gene: DPAGT1 were changed from Congenital disorder of glycosylation, type Ij, MIM#614750 to Congenital disorder of glycosylation, type Ij, MIM# 608093; DPAGT1-CDG MONDO:0011964; Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750
BabyScreen+ newborn screening v0.540 DPAGT1 Zornitza Stark reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ij, MIM# 608093, DPAGT1-CDG MONDO:0011964, Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.540 DOLK Zornitza Stark Marked gene: DOLK as ready
BabyScreen+ newborn screening v0.539 DLD Zornitza Stark Marked gene: DLD as ready
BabyScreen+ newborn screening v0.538 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
BabyScreen+ newborn screening v0.536 DGUOK Zornitza Stark Marked gene: DGUOK as ready
BabyScreen+ newborn screening v0.534 DDC Zornitza Stark Marked gene: DDC as ready
BabyScreen+ newborn screening v0.534 DDC Zornitza Stark reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aromatic L-amino acid decarboxylase deficiency MIM# 608643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.534 DGAT1 Zornitza Stark Marked gene: DGAT1 as ready
BabyScreen+ newborn screening v0.534 DGAT1 Zornitza Stark reviewed gene: DGAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diarrhoea 7, protein-losing enteropathy type, MIM# 615863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.534 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
BabyScreen+ newborn screening v0.534 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from D-2-hydroxyglutaric aciduria to D-2-hydroxyglutaric aciduria MIM#600721
BabyScreen+ newborn screening v0.532 D2HGDH Zornitza Stark reviewed gene: D2HGDH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: D-2-hydroxyglutaric aciduria MIM#600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.532 CYP27B1 Zornitza Stark Marked gene: CYP27B1 as ready
BabyScreen+ newborn screening v0.531 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
BabyScreen+ newborn screening v0.529 CYP17A1 Zornitza Stark Marked gene: CYP17A1 as ready
BabyScreen+ newborn screening v0.529 CYP11B2 Zornitza Stark Marked gene: CYP11B2 as ready
BabyScreen+ newborn screening v0.529 CYP11A1 Zornitza Stark reviewed gene: CYP11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, MIM# 613743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.529 CYP11B1 Zornitza Stark Marked gene: CYP11B1 as ready
BabyScreen+ newborn screening v0.528 CUBN Zornitza Stark Marked gene: CUBN as ready
BabyScreen+ newborn screening v0.528 CTSD Zornitza Stark Marked gene: CTSD as ready
BabyScreen+ newborn screening v0.526 CTNS Zornitza Stark Marked gene: CTNS as ready
BabyScreen+ newborn screening v0.525 CPS1 Zornitza Stark Marked gene: CPS1 as ready
BabyScreen+ newborn screening v0.524 CPS1 Zornitza Stark reviewed gene: CPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28281899; Phenotypes: Carbamoylphosphate synthetase I deficiency MIM#237300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.524 COQ9 Zornitza Stark Marked gene: COQ9 as ready
BabyScreen+ newborn screening v0.523 COQ9 Zornitza Stark reviewed gene: COQ9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 5, MIM#614654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.523 DGAT1 John Christodoulou reviewed gene: DGAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31778854; Phenotypes: intractable diarrhoea; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.523 CYP27A1 John Christodoulou reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: diarrhoea, cataracts, xanthomas, progressive ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.523 CYP11B2 John Christodoulou reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: primary hyperaldosteronism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.523 CUBN John Christodoulou commented on gene: CUBN: defect of intestinal vitamin B12 absorption; treatable with pharmacological doses of parenteral vitamin B12
BabyScreen+ newborn screening v0.523 VPS33B Zornitza Stark Marked gene: VPS33B as ready
BabyScreen+ newborn screening v0.523 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from Arthrogryposis renal dysfunction cholestasis syndrome to Arthrogryposis, renal dysfunction, and cholestasis MIM#208085
BabyScreen+ newborn screening v0.520 VPS45 Zornitza Stark Marked gene: VPS45 as ready
BabyScreen+ newborn screening v0.519 WAS Zornitza Stark Marked gene: WAS as ready
BabyScreen+ newborn screening v0.518 WDR62 Zornitza Stark Marked gene: WDR62 as ready
BabyScreen+ newborn screening v0.518 WDR62 Zornitza Stark Phenotypes for gene: WDR62 were changed from Microcephaly 2, primary, autosomal recessive, with or without cortical malformations to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations MIM#604317
BabyScreen+ newborn screening v0.515 WFS1 Zornitza Stark Marked gene: WFS1 as ready
BabyScreen+ newborn screening v0.512 WHRN Zornitza Stark Marked gene: WHRN as ready
BabyScreen+ newborn screening v0.512 WRAP53 Zornitza Stark Marked gene: WRAP53 as ready
BabyScreen+ newborn screening v0.511 WRN Zornitza Stark Marked gene: WRN as ready
BabyScreen+ newborn screening v0.508 XIAP Zornitza Stark Marked gene: XIAP as ready
BabyScreen+ newborn screening v0.507 SCN3A Seb Lunke Marked gene: SCN3A as ready
BabyScreen+ newborn screening v0.507 SCN3A Seb Lunke Phenotypes for gene: SCN3A were changed from Developmental and epileptic encephalopathy 62, MIM# 617938 to Epileptic encephalopathy, early infantile, 62, MIM# 617938
BabyScreen+ newborn screening v0.505 SCN3A Seb Lunke reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34081427; Phenotypes: Epileptic encephalopathy, early infantile, 62, MIM# 617938; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.505 SCN2A Seb Lunke Marked gene: SCN2A as ready
BabyScreen+ newborn screening v0.505 SCN2A Seb Lunke changed review comment from: Established gene-disease association. Childhood onset, severe neurological disorder.

Treatment: Phenytoin; high dose carbamazepine

Non-genetic confirmatory test: not available; to: Established gene-disease association.

Childhood onset, severe neurological disorder.

Treatment: Phenytoin; high dose carbamazepine

Non-genetic confirmatory test: not available
BabyScreen+ newborn screening v0.505 SCN1A Seb Lunke Marked gene: SCN1A as ready
BabyScreen+ newborn screening v0.505 SCN1A Seb Lunke Phenotypes for gene: SCN1A were changed from Dravet syndrome, MIM#604403; Developmental and epileptic encephalopathy 6B, non-Dravet , MIM#619317 to Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM#604403; Developmental and epileptic encephalopathy 6B, non-Dravet , MIM#619317
BabyScreen+ newborn screening v0.503 SCN1A Seb Lunke reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301494; Phenotypes: Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.503 VPS33B Lilian Downie reviewed gene: VPS33B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 15052268, 15052268, 18853461; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis MIM#208085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.503 WDR62 Lilian Downie reviewed gene: WDR62: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 35188728; Phenotypes: Microcephaly 2, primary, autosomal recessive, with or without cortical malformations MIM#604317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.503 WHRN Lilian Downie commented on gene: WHRN: Definitive gene disease association Usher, moderate evidence it can also cause a non syndromic hearing loss phenotype.
Congenital hearing impairment, childhood onset visual loss
Treatment supportive, clinical trials for retinitis pigmentosa

*I think we should keep hearing loss genes on as it's part of traditional newborn screening*
BabyScreen+ newborn screening v0.503 GAA Zornitza Stark Marked gene: GAA as ready
BabyScreen+ newborn screening v0.502 GAA Alison Yeung changed review comment from: Well establishes gene-disease association

Onset: Classic infantile form causes cardiomyopathy and severe hypotonia in infancy (<1 year); Late-onset form causes severe weakness and respiratory insufficiency with onset after 12 months; Adult form presents with progressive myopathy

Severity: Infantile form fatal in first year of life if untreated

Treatment: Enzyme replacement therapy with alglucosidase alfa prior to 6 months of age prolongs survival, reduces cardiac size and allows acquisition of motor skills; to: Well establishes gene-disease association

Onset: Classic infantile form causes cardiomyopathy and severe hypotonia in infancy (<1 year); Late-onset form causes severe weakness and respiratory insufficiency with onset after 12 months; Adult form presents with progressive myopathy

Severity: Infantile form fatal in first year of life if untreated

Treatment: Enzyme replacement therapy with alglucosidase alfa prior to 6 months of age prolongs survival, reduces cardiac size and allows acquisition of motor skills

Non-molecular confirmatory test: enzyme activity analysis
BabyScreen+ newborn screening v0.502 G6PD Zornitza Stark Marked gene: G6PD as ready
BabyScreen+ newborn screening v0.502 SCN11A Seb Lunke Marked gene: SCN11A as ready
BabyScreen+ newborn screening v0.502 SCN11A Seb Lunke Phenotypes for gene: SCN11A were changed from Episodic pain syndrome to Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548
BabyScreen+ newborn screening v0.500 SCN11A Seb Lunke reviewed gene: SCN11A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.500 SBDS Seb Lunke Marked gene: SBDS as ready
BabyScreen+ newborn screening v0.498 BLNK Zornitza Stark Marked gene: BLNK as ready
BabyScreen+ newborn screening v0.497 C5 Zornitza Stark Marked gene: C5 as ready
BabyScreen+ newborn screening v0.497 SAMHD1 Seb Lunke Marked gene: SAMHD1 as ready
BabyScreen+ newborn screening v0.497 SAMHD1 Seb Lunke Phenotypes for gene: SAMHD1 were changed from Aicardi-Goutieres syndrome to Aicardi-Goutieres syndrome 5, MIM# 612952
BabyScreen+ newborn screening v0.495 SAMHD1 Seb Lunke reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32877590; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.495 BSND Zornitza Stark Marked gene: BSND as ready
BabyScreen+ newborn screening v0.495 BSND Zornitza Stark Phenotypes for gene: BSND were changed from Bartter syndrome with sensorineural deafness to Bartter syndrome, type 4a, MIM# 602522
BabyScreen+ newborn screening v0.494 BSND Zornitza Stark reviewed gene: BSND: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 4a, MIM# 602522; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.494 SALL1 Seb Lunke Marked gene: SALL1 as ready
BabyScreen+ newborn screening v0.494 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
BabyScreen+ newborn screening v0.492 SACS Seb Lunke Marked gene: SACS as ready
BabyScreen+ newborn screening v0.492 SACS Seb Lunke Phenotypes for gene: SACS were changed from Spastic ataxia Charlevoix-Saguenay type to Spastic ataxia, Charlevoix-Saguenay type MIM#270550
BabyScreen+ newborn screening v0.490 SACS Seb Lunke reviewed gene: SACS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic ataxia, Charlevoix-Saguenay type MIM#270550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
BabyScreen+ newborn screening v0.490 BRIP1 Zornitza Stark Marked gene: BRIP1 as ready
BabyScreen+ newborn screening v0.490 BMPR1A Zornitza Stark Marked gene: BMPR1A as ready
BabyScreen+ newborn screening v0.489 BLM Zornitza Stark Marked gene: BLM as ready
BabyScreen+ newborn screening v0.487 ADGRV1 Zornitza Stark Marked gene: ADGRV1 as ready
BabyScreen+ newborn screening v0.486 ACADVL Zornitza Stark Marked gene: ACADVL as ready
BabyScreen+ newborn screening v0.485 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
BabyScreen+ newborn screening v0.485 ACAD9 Zornitza Stark reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20, MIM# 611126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.485 ACTG1 Zornitza Stark Marked gene: ACTG1 as ready
BabyScreen+ newborn screening v0.485 ACTG1 Zornitza Stark Phenotypes for gene: ACTG1 were changed from Baraitser-Winter syndrome; Deafness, autosomal dominant to Baraitser-Winter syndrome 2MIM#614583; Deafness, autosomal dominant 20/26 MIM#604717
BabyScreen+ newborn screening v0.483 ACTG1 Zornitza Stark reviewed gene: ACTG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Baraitser-Winter syndrome 2MIM#614583, Deafness, autosomal dominant 20/26 MIM#604717; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.483 ACAD8 Zornitza Stark Marked gene: ACAD8 as ready
BabyScreen+ newborn screening v0.481 OSMR Zornitza Stark Marked gene: OSMR as ready
BabyScreen+ newborn screening v0.481 OSMR Zornitza Stark Phenotypes for gene: OSMR were changed from Amyloidosis, primary cutaneous to Amyloidosis, primary localized cutaneous, 1 - MIM#105250
BabyScreen+ newborn screening v0.479 OSMR Zornitza Stark reviewed gene: OSMR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, primary localized cutaneous, 1 - MIM#105250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.479 ORC1 Zornitza Stark Marked gene: ORC1 as ready
BabyScreen+ newborn screening v0.477 OPA1 Zornitza Stark Marked gene: OPA1 as ready
BabyScreen+ newborn screening v0.477 OPA1 Zornitza Stark Phenotypes for gene: OPA1 were changed from Optic atrophy 1 to Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)MIM# 616896; Behr syndrome MIM#210000, AR; Optic atrophy 1, MIM#165500; Optic atrophy plus syndrome, MIM# 125250
BabyScreen+ newborn screening v0.474 OPA1 Zornitza Stark reviewed gene: OPA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)MIM# 616896, Behr syndrome MIM#210000, AR, Optic atrophy 1, MIM#165500, Optic atrophy plus syndrome, MIM# 125250; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.474 OFD1 Zornitza Stark Marked gene: OFD1 as ready
BabyScreen+ newborn screening v0.472 OCRL Zornitza Stark Marked gene: OCRL as ready
BabyScreen+ newborn screening v0.470 OCA2 Zornitza Stark Marked gene: OCA2 as ready
BabyScreen+ newborn screening v0.467 OBSL1 Zornitza Stark Marked gene: OBSL1 as ready
BabyScreen+ newborn screening v0.465 NTRK1 Zornitza Stark Marked gene: NTRK1 as ready
BabyScreen+ newborn screening v0.464 NSD1 Zornitza Stark Marked gene: NSD1 as ready
BabyScreen+ newborn screening v0.462 NR5A1 Zornitza Stark Marked gene: NR5A1 as ready
BabyScreen+ newborn screening v0.461 NR3C2 Zornitza Stark Marked gene: NR3C2 as ready
BabyScreen+ newborn screening v0.461 NR0B1 Zornitza Stark Marked gene: NR0B1 as ready
BabyScreen+ newborn screening v0.460 NPHS1 Zornitza Stark Marked gene: NPHS1 as ready
BabyScreen+ newborn screening v0.458 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
BabyScreen+ newborn screening v0.456 NPHP3 Zornitza Stark Marked gene: NPHP3 as ready
BabyScreen+ newborn screening v0.454 OSMR David Amor reviewed gene: OSMR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, primary localized cutaneous, 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.454 NPHP1 Zornitza Stark Marked gene: NPHP1 as ready
BabyScreen+ newborn screening v0.452 NPC2 Zornitza Stark Marked gene: NPC2 as ready
BabyScreen+ newborn screening v0.451 NPC1 Zornitza Stark Marked gene: NPC1 as ready
BabyScreen+ newborn screening v0.450 NOTCH3 Zornitza Stark Marked gene: NOTCH3 as ready
BabyScreen+ newborn screening v0.450 NOTCH3 Zornitza Stark Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM# 125310
BabyScreen+ newborn screening v0.448 NOTCH3 Zornitza Stark reviewed gene: NOTCH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM# 125310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.448 NOTCH2 Zornitza Stark Marked gene: NOTCH2 as ready
BabyScreen+ newborn screening v0.446 NOG Zornitza Stark Marked gene: NOG as ready
BabyScreen+ newborn screening v0.446 NOG Zornitza Stark Phenotypes for gene: NOG were changed from Symphalangism, proximal, 1A to Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570)
BabyScreen+ newborn screening v0.444 NOG Zornitza Stark reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brachydactyly, type B2 - MIM#611377, Multiple synostoses syndrome 1 (MIM#186500), Stapes ankylosis with broad thumbs and toes (MIM#184460), Symphalangism, proximal, 1A (MIM#185800), Tarsal-carpal coalition syndrome (MIM#186570); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.444 NNT Zornitza Stark Marked gene: NNT as ready
BabyScreen+ newborn screening v0.443 NKX2-1 Zornitza Stark Marked gene: NKX2-1 as ready
BabyScreen+ newborn screening v0.442 NIPBL Zornitza Stark Marked gene: NIPBL as ready
BabyScreen+ newborn screening v0.440 NIPAL4 Zornitza Stark Marked gene: NIPAL4 as ready
BabyScreen+ newborn screening v0.438 NHLRC1 Zornitza Stark Marked gene: NHLRC1 as ready
BabyScreen+ newborn screening v0.436 NHEJ1 Zornitza Stark Marked gene: NHEJ1 as ready
BabyScreen+ newborn screening v0.436 NHEJ1 Zornitza Stark reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.436 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
BabyScreen+ newborn screening v0.434 NF2 Zornitza Stark Marked gene: NF2 as ready
BabyScreen+ newborn screening v0.432 NF1 Zornitza Stark Marked gene: NF1 as ready
BabyScreen+ newborn screening v0.430 NEUROG3 Zornitza Stark Marked gene: NEUROG3 as ready
BabyScreen+ newborn screening v0.430 NEUROG3 Zornitza Stark reviewed gene: NEUROG3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diarrhoea 4, malabsorptive, congenital, MIM# 610370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.430 NEU1 Zornitza Stark Marked gene: NEU1 as ready
BabyScreen+ newborn screening v0.428 NEK8 Zornitza Stark Marked gene: NEK8 as ready
BabyScreen+ newborn screening v0.427 NEK1 Zornitza Stark Marked gene: NEK1 as ready
BabyScreen+ newborn screening v0.426 NEFL Zornitza Stark Marked gene: NEFL as ready
BabyScreen+ newborn screening v0.426 NEFL Zornitza Stark Phenotypes for gene: NEFL were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, dominant intermediate G, MIM# 617882; Charcot-Marie-Tooth disease, type 1F, MIM# 607734; Charcot-Marie-Tooth disease, type 2E 607684
BabyScreen+ newborn screening v0.423 NEFL Zornitza Stark reviewed gene: NEFL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate G, MIM# 617882, Charcot-Marie-Tooth disease, type 1F, MIM# 607734, Charcot-Marie-Tooth disease, type 2E 607684; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.423 NEB Zornitza Stark Marked gene: NEB as ready
BabyScreen+ newborn screening v0.423 NEB Zornitza Stark Phenotypes for gene: NEB were changed from Nemaline myopathy to Nemaline myopathy 2, autosomal recessive 256030; Arthrogryposis multiplex congenita 6, MIM# 619334
BabyScreen+ newborn screening v0.421 NEB Zornitza Stark reviewed gene: NEB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 2, autosomal recessive 256030, Arthrogryposis multiplex congenita 6, MIM# 619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.421 NDP Zornitza Stark Marked gene: NDP as ready
BabyScreen+ newborn screening v0.419 NCF2 Zornitza Stark Marked gene: NCF2 as ready
BabyScreen+ newborn screening v0.418 NCF1 Zornitza Stark Marked gene: NCF1 as ready
BabyScreen+ newborn screening v0.417 NBN Zornitza Stark Marked gene: NBN as ready
BabyScreen+ newborn screening v0.416 NAGS Zornitza Stark Marked gene: NAGS as ready
BabyScreen+ newborn screening v0.416 NAGLU Zornitza Stark Marked gene: NAGLU as ready
BabyScreen+ newborn screening v0.416 NAGLU Zornitza Stark Phenotypes for gene: NAGLU were changed from Sanfilippo syndrome type B to Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920
BabyScreen+ newborn screening v0.415 NAGLU Zornitza Stark reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.415 NAGA Zornitza Stark Marked gene: NAGA as ready
BabyScreen+ newborn screening v0.413 MYO9A Zornitza Stark Marked gene: MYO9A as ready
BabyScreen+ newborn screening v0.412 MYO7A Zornitza Stark Marked gene: MYO7A as ready
BabyScreen+ newborn screening v0.411 MYO6 Zornitza Stark Marked gene: MYO6 as ready
BabyScreen+ newborn screening v0.409 MYO3A Zornitza Stark Marked gene: MYO3A as ready
BabyScreen+ newborn screening v0.409 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from Sensorineural hearing loss to Deafness, autosomal recessive 30, MIM:607101
BabyScreen+ newborn screening v0.407 MYO15A Zornitza Stark Marked gene: MYO15A as ready
BabyScreen+ newborn screening v0.407 MYO15A Zornitza Stark Phenotypes for gene: MYO15A were changed from Sensorineural hearing loss to Deafness, autosomal recessive 3, MIM# 600316
BabyScreen+ newborn screening v0.406 MYH9 Zornitza Stark Marked gene: MYH9 as ready
BabyScreen+ newborn screening v0.406 MYH9 Zornitza Stark Phenotypes for gene: MYH9 were changed from Macrothrombocytopenia and progressive sensorineural deafness to Deafness, autosomal dominant 17, MIM# 603622; Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100
BabyScreen+ newborn screening v0.404 MYH9 Zornitza Stark reviewed gene: MYH9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 17, MIM# 603622, Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.404 MYH7 Zornitza Stark Marked gene: MYH7 as ready
BabyScreen+ newborn screening v0.402 MYH7 Zornitza Stark reviewed gene: MYH7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1S, MIM# 613426 MONDO:0013262, Cardiomyopathy, hypertrophic, 1, MIM# 192600, Laing distal myopathy, MIM# 160500, Myopathy, myosin storage, autosomal dominant, MIM# 608358, Myopathy, myosin storage, autosomal recessive, MIM# 255160; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.402 MYH3 Zornitza Stark Marked gene: MYH3 as ready
BabyScreen+ newborn screening v0.402 MYH3 Zornitza Stark Phenotypes for gene: MYH3 were changed from Arthrogryposis, distal to Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469
BabyScreen+ newborn screening v0.399 MYH3 Zornitza Stark reviewed gene: MYH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436, Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110, Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.399 MYH2 Zornitza Stark Marked gene: MYH2 as ready
BabyScreen+ newborn screening v0.397 MYH14 Zornitza Stark Marked gene: MYH14 as ready
BabyScreen+ newborn screening v0.397 MYH14 Zornitza Stark Phenotypes for gene: MYH14 were changed from Deafness, autosomal dominant to Deafness, autosomal dominant 4A, MIM# 600652; Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369
BabyScreen+ newborn screening v0.394 MYH14 Zornitza Stark reviewed gene: MYH14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 4A, MIM# 600652, Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.394 MYCN Zornitza Stark Marked gene: MYCN as ready
BabyScreen+ newborn screening v0.392 MYBPC1 Zornitza Stark Marked gene: MYBPC1 as ready
BabyScreen+ newborn screening v0.391 MYBPC1 Zornitza Stark reviewed gene: MYBPC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 1B 614335, Lethal congenital contracture syndrome 4, MIM# 614915; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.391 MVK Zornitza Stark Marked gene: MVK as ready
BabyScreen+ newborn screening v0.389 XPA Zornitza Stark Marked gene: XPA as ready
BabyScreen+ newborn screening v0.388 XPC Zornitza Stark Marked gene: XPC as ready
BabyScreen+ newborn screening v0.386 MUTYH Zornitza Stark Marked gene: MUTYH as ready
BabyScreen+ newborn screening v0.384 MYSM1 Zornitza Stark Marked gene: MYSM1 as ready
BabyScreen+ newborn screening v0.384 MYSM1 Zornitza Stark reviewed gene: MYSM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bone marrow failure syndrome 4, MIM#618116; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.384 MUSK Zornitza Stark Marked gene: MUSK as ready
BabyScreen+ newborn screening v0.384 MTTP Zornitza Stark Marked gene: MTTP as ready
BabyScreen+ newborn screening v0.383 MTRR Zornitza Stark Marked gene: MTRR as ready
BabyScreen+ newborn screening v0.382 MSX2 Zornitza Stark Marked gene: MSX2 as ready
BabyScreen+ newborn screening v0.382 MSX2 Zornitza Stark Phenotypes for gene: MSX2 were changed from Parietal foramina 1 to Craniosynostosis 2 (MIM#604757); Parietal foramina 1 (MIM#168500); Parietal foramina with cleidocranial dysplasia (MIM#168550)
BabyScreen+ newborn screening v0.380 MSX2 Zornitza Stark reviewed gene: MSX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis 2 (MIM#604757), Parietal foramina 1 (MIM#168500), Parietal foramina with cleidocranial dysplasia (MIM#168550); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.380 MRAP Zornitza Stark Marked gene: MRAP as ready
BabyScreen+ newborn screening v0.380 MTR Zornitza Stark Marked gene: MTR as ready
BabyScreen+ newborn screening v0.378 MTM1 Zornitza Stark Marked gene: MTM1 as ready
BabyScreen+ newborn screening v0.378 MTM1 Zornitza Stark Phenotypes for gene: MTM1 were changed from Myotubular myopathy, X-linked to Myopathy, centronuclear, X-linked, MIM# 310400
BabyScreen+ newborn screening v0.376 MTM1 Zornitza Stark reviewed gene: MTM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.376 MPZ Zornitza Stark Marked gene: MPZ as ready
BabyScreen+ newborn screening v0.376 MPZ Zornitza Stark Phenotypes for gene: MPZ were changed from Charcot-Marie-Tooth disease to Charcot Marie Tooth disease, dominant intermediate D, 60779; Neuropathy, congenital hypomyelinating, 605253; Charcot Marie Tooth disease, type 2J, 607736; Dejerine Sottas disease, 145900; Charcot Marie Tooth disease, type 1B, 118200; Charcot Marie Tooth disease, type 2I, 607677
BabyScreen+ newborn screening v0.373 MPZ Zornitza Stark reviewed gene: MPZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot Marie Tooth disease, dominant intermediate D, 60779, Neuropathy, congenital hypomyelinating, 605253, Charcot Marie Tooth disease, type 2J, 607736, Dejerine Sottas disease, 145900, Charcot Marie Tooth disease, type 1B, 118200, Charcot Marie Tooth disease, type 2I, 607677; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.373 MPV17 Zornitza Stark Marked gene: MPV17 as ready
BabyScreen+ newborn screening v0.371 MPL Zornitza Stark Marked gene: MPL as ready
BabyScreen+ newborn screening v0.371 MPL Zornitza Stark Phenotypes for gene: MPL were changed from Thrombocytopaenia, congenital amegakaryocytic, MIM# 604498 to Thrombocytopenia, congenital amegakaryocytic, MIM# 604498
BabyScreen+ newborn screening v0.370 MPL Zornitza Stark Phenotypes for gene: MPL were changed from Amegakaryocytic thrombocytopaenia, congenital to Thrombocytopaenia, congenital amegakaryocytic, MIM# 604498
BabyScreen+ newborn screening v0.368 MPL Zornitza Stark reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia, congenital amegakaryocytic, MIM# 604498; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.368 MPI Zornitza Stark Marked gene: MPI as ready
BabyScreen+ newborn screening v0.366 MPDU1 Zornitza Stark Marked gene: MPDU1 as ready
BabyScreen+ newborn screening v0.365 MOCS2 Zornitza Stark Marked gene: MOCS2 as ready
BabyScreen+ newborn screening v0.363 MOCS1 Zornitza Stark Marked gene: MOCS1 as ready
BabyScreen+ newborn screening v0.362 MLYCD Zornitza Stark Marked gene: MLYCD as ready
BabyScreen+ newborn screening v0.362 MLYCD Zornitza Stark Phenotypes for gene: MLYCD were changed from Malonyl-CoA decarboxylase deficiency to Malonyl-CoA decarboxylase deficiency, MIM# 248360
BabyScreen+ newborn screening v0.361 MLYCD Zornitza Stark reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Malonyl-CoA decarboxylase deficiency, MIM# 248360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.361 ZAP70 Zornitza Stark Marked gene: ZAP70 as ready
BabyScreen+ newborn screening v0.359 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
BabyScreen+ newborn screening v0.356 ZIC2 Zornitza Stark Marked gene: ZIC2 as ready
BabyScreen+ newborn screening v0.353 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
BabyScreen+ newborn screening v0.353 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from Heterotaxy to X linked heterotaxy and congenital heart defects MIM:306955
BabyScreen+ newborn screening v0.350 ZMPSTE24 Zornitza Stark Marked gene: ZMPSTE24 as ready
BabyScreen+ newborn screening v0.347 ZNF469 Zornitza Stark Marked gene: ZNF469 as ready
BabyScreen+ newborn screening v0.344 MLC1 Zornitza Stark Marked gene: MLC1 as ready
BabyScreen+ newborn screening v0.342 MKS1 Zornitza Stark Marked gene: MKS1 as ready
BabyScreen+ newborn screening v0.342 MKS1 Zornitza Stark Phenotypes for gene: MKS1 were changed from Meckel syndrome to Joubert syndrome 28, MIM# 617121 MONDO:0014928; Meckel syndrome 1, MIM# 249000 MONDO:0009571; Bardet-Biedl syndrome 13, MIM# 615990 MONDO:0014441
BabyScreen+ newborn screening v0.340 MKS1 Zornitza Stark reviewed gene: MKS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 28, MIM# 617121 MONDO:0014928, Meckel syndrome 1, MIM# 249000 MONDO:0009571, Bardet-Biedl syndrome 13, MIM# 615990 MONDO:0014441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.340 MKKS Zornitza Stark Marked gene: MKKS as ready
BabyScreen+ newborn screening v0.340 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700
BabyScreen+ newborn screening v0.338 MKKS Zornitza Stark reviewed gene: MKKS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome, MIM# 236700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.338 LAMB3 Zornitza Stark Marked gene: LAMB3 as ready
BabyScreen+ newborn screening v0.335 LAMA2 Zornitza Stark Marked gene: LAMA2 as ready
BabyScreen+ newborn screening v0.335 LAMA2 Zornitza Stark Phenotypes for gene: LAMA2 were changed from Muscular dystrophy, congenital merosin-deficient to Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855
BabyScreen+ newborn screening v0.333 MITF Zornitza Stark Marked gene: MITF as ready
BabyScreen+ newborn screening v0.333 MITF Zornitza Stark Phenotypes for gene: MITF were changed from Waardenburg syndrome to Waardenburg syndrome, type 2A, MIM# 193510; Deafness
BabyScreen+ newborn screening v0.331 MITF Zornitza Stark reviewed gene: MITF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome, type 2A, MIM# 193510, Deafness; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.331 MGP Zornitza Stark Marked gene: MGP as ready
BabyScreen+ newborn screening v0.329 MGAT2 Zornitza Stark Marked gene: MGAT2 as ready
BabyScreen+ newborn screening v0.328 MFSD8 Zornitza Stark Marked gene: MFSD8 as ready
BabyScreen+ newborn screening v0.325 MFN2 Zornitza Stark Marked gene: MFN2 as ready
BabyScreen+ newborn screening v0.325 MFN2 Zornitza Stark Phenotypes for gene: MFN2 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087; Hereditary motor and sensory neuropathy VIA, OMIM #601152
BabyScreen+ newborn screening v0.322 MFN2 Zornitza Stark reviewed gene: MFN2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260, Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087, Hereditary motor and sensory neuropathy VIA, OMIM #601152; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.322 MEN1 Zornitza Stark Marked gene: MEN1 as ready
BabyScreen+ newborn screening v0.321 MEGF10 Zornitza Stark Marked gene: MEGF10 as ready
BabyScreen+ newborn screening v0.321 MEGF10 Zornitza Stark Phenotypes for gene: MEGF10 were changed from Myopathy, areflexia, respiratory distress, and dysphagia, early-onset to Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399
BabyScreen+ newborn screening v0.319 MEGF10 Zornitza Stark reviewed gene: MEGF10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.319 MEFV Zornitza Stark Marked gene: MEFV as ready
BabyScreen+ newborn screening v0.318 MED25 Zornitza Stark Marked gene: MED25 as ready
BabyScreen+ newborn screening v0.317 MED12 Zornitza Stark Marked gene: MED12 as ready
BabyScreen+ newborn screening v0.317 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from Intellectual disability to Ohdo syndrome, X-linked MIM#300895; Lujan-Fryns syndrome MIM#309520; Opitz-Kaveggia syndrome MIM#305450; Hardikar syndrome, MIM# 301068
BabyScreen+ newborn screening v0.315 MED12 Zornitza Stark reviewed gene: MED12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ohdo syndrome, X-linked MIM#300895, Lujan-Fryns syndrome MIM#309520, Opitz-Kaveggia syndrome MIM#305450, Hardikar syndrome, MIM# 301068; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.315 MECP2 Zornitza Stark Marked gene: MECP2 as ready
BabyScreen+ newborn screening v0.315 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from Rett syndrome to MECP2-related disorders Rett syndrome, MIM# 312750 Mental retardation, X-linked, syndromic 13, MIM# 300055
BabyScreen+ newborn screening v0.312 MECP2 Zornitza Stark reviewed gene: MECP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: MECP2-related disorders Rett syndrome, MIM# 312750 Mental retardation, X-linked, syndromic 13, MIM# 300055; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.312 MCPH1 Zornitza Stark Marked gene: MCPH1 as ready
BabyScreen+ newborn screening v0.312 MCPH1 Zornitza Stark Phenotypes for gene: MCPH1 were changed from Microcephaly 1, primary, autosomal recessive to Microcephaly 1, primary, autosomal recessive, MIM# 251200
BabyScreen+ newborn screening v0.311 MCPH1 Zornitza Stark reviewed gene: MCPH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 1, primary, autosomal recessive, MIM# 251200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.310 COQ8B Zornitza Stark Marked gene: COQ8B as ready
BabyScreen+ newborn screening v0.310 COQ8A Zornitza Stark Marked gene: COQ8A as ready
BabyScreen+ newborn screening v0.309 COQ8A Zornitza Stark reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32337771; Phenotypes: Coenzyme Q10 deficiency, primary, 4 MIM#612016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.309 COQ7 Zornitza Stark Marked gene: COQ7 as ready
BabyScreen+ newborn screening v0.309 COQ7 Zornitza Stark reviewed gene: COQ7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 8 MIM#616733; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.309 COQ4 Zornitza Stark Marked gene: COQ4 as ready
BabyScreen+ newborn screening v0.309 COQ4 Zornitza Stark reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.309 COLQ Zornitza Stark Marked gene: COLQ as ready
BabyScreen+ newborn screening v0.309 CLN8 Zornitza Stark Phenotypes for gene: CLN8 were changed from Ceroid lipofuscinosis, neuronal, 8, MIM# 600143 Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003 to Ceroid lipofuscinosis, neuronal, 8, MIM# 600143; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003
BabyScreen+ newborn screening v0.308 CLN8 Zornitza Stark edited their review of gene: CLN8: Changed phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003
BabyScreen+ newborn screening v0.308 CLN8 Zornitza Stark Marked gene: CLN8 as ready
BabyScreen+ newborn screening v0.308 CLN8 Zornitza Stark Phenotypes for gene: CLN8 were changed from Ceroid lipofuscinosis, neuronal, 8 to Ceroid lipofuscinosis, neuronal, 8, MIM# 600143 Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003
BabyScreen+ newborn screening v0.305 CLN8 Zornitza Stark reviewed gene: CLN8: Rating: RED; Mode of pathogenicity: None; Publications: 33242182; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143 Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.305 CLN6 Zornitza Stark Marked gene: CLN6 as ready
BabyScreen+ newborn screening v0.302 CLN5 Zornitza Stark Marked gene: CLN5 as ready
BabyScreen+ newborn screening v0.300 CLN3 Zornitza Stark Marked gene: CLN3 as ready
BabyScreen+ newborn screening v0.298 CHRNG Zornitza Stark Marked gene: CHRNG as ready
BabyScreen+ newborn screening v0.298 CHRNG Zornitza Stark Phenotypes for gene: CHRNG were changed from Pterygium syndrome to Escobar syndrome, MIM# 265000; Multiple pterygium syndrome, lethal type, MIM# 253290
BabyScreen+ newborn screening v0.296 CHRNG Zornitza Stark reviewed gene: CHRNG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Escobar syndrome, MIM# 265000, Multiple pterygium syndrome, lethal type, MIM# 253290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.296 CHRNE Zornitza Stark Marked gene: CHRNE as ready
BabyScreen+ newborn screening v0.295 CHRNE Zornitza Stark changed review comment from: Well established association with multiple subtypes of congenital myasthenia, both mono- and bi-allelic variants reported.

Severe disorder, congenital.; to: Well established association with multiple subtypes of congenital myasthenia, both mono- and bi-allelic variants reported.

Severe disorder, congenital.

Treatment available.
BabyScreen+ newborn screening v0.295 CHRND Zornitza Stark changed review comment from: Well established gene-disease association.

Severe disorder, perinatal onset.

Treatment: 3,4-diaminopyridine, acetylcholine-esterase inhibitors; to: Well established gene-disease association for bi-allelic variants. Single individual only with mono-allelic variant reported.

Severe disorder, perinatal onset.

Treatment: 3,4-diaminopyridine, acetylcholine-esterase inhibitors
BabyScreen+ newborn screening v0.295 CHRND Zornitza Stark Marked gene: CHRND as ready
BabyScreen+ newborn screening v0.293 SLC5A2 Zornitza Stark Marked gene: SLC5A2 as ready
BabyScreen+ newborn screening v0.290 CHRNA1 Zornitza Stark Marked gene: CHRNA1 as ready
BabyScreen+ newborn screening v0.288 CHAT Zornitza Stark Marked gene: CHAT as ready
BabyScreen+ newborn screening v0.288 CA5A Zornitza Stark Marked gene: CA5A as ready
BabyScreen+ newborn screening v0.288 CA5A Zornitza Stark reviewed gene: CA5A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperammonemia due to carbonic anhydrase VA deficiency, 615751; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.288 BTK Zornitza Stark Marked gene: BTK as ready
BabyScreen+ newborn screening v0.288 BCS1L Zornitza Stark Marked gene: BCS1L as ready
BabyScreen+ newborn screening v0.286 BCKDK Zornitza Stark Marked gene: BCKDK as ready
BabyScreen+ newborn screening v0.286 AUH Zornitza Stark Marked gene: AUH as ready
BabyScreen+ newborn screening v0.284 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
BabyScreen+ newborn screening v0.282 ATP7B Zornitza Stark Marked gene: ATP7B as ready
BabyScreen+ newborn screening v0.281 ASL Zornitza Stark Marked gene: ASL as ready
BabyScreen+ newborn screening v0.281 ASL Zornitza Stark reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Argininosuccinic aciduria MIM#207900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.281 ARSB Zornitza Stark Marked gene: ARSB as ready
BabyScreen+ newborn screening v0.281 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.281 ARSB Zornitza Stark Phenotypes for gene: ARSB were changed from Mucopolysaccharidosis type VI (Maroteaux-Lamy) to Mucopolysaccharidosis VI (MPS6, MIM# 253200
BabyScreen+ newborn screening v0.280 ARSB Zornitza Stark Publications for gene: ARSB were set to
BabyScreen+ newborn screening v0.279 ARSB Zornitza Stark Tag treatable tag was added to gene: ARSB.
Tag clinical trial tag was added to gene: ARSB.
BabyScreen+ newborn screening v0.279 ARSB Zornitza Stark reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31142378; Phenotypes: Mucopolysaccharidosis VI (MPS6, MIM# 253200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.279 ARG1 Zornitza Stark Marked gene: ARG1 as ready
BabyScreen+ newborn screening v0.279 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.279 ARG1 Zornitza Stark Tag treatable tag was added to gene: ARG1.
BabyScreen+ newborn screening v0.279 ARG1 Zornitza Stark reviewed gene: ARG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Argininaemia MIM#207800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.279 AHCY Zornitza Stark Marked gene: AHCY as ready
BabyScreen+ newborn screening v0.278 AGL Zornitza Stark Marked gene: AGL as ready
BabyScreen+ newborn screening v0.277 SMN1 Zornitza Stark Marked gene: SMN1 as ready
BabyScreen+ newborn screening v0.277 SMN1 Zornitza Stark Phenotypes for gene: SMN1 were changed from Spinal muscular atrophy type 1, 253300; Spinal muscular atrophy type 2, 253550; Spinal muscular atrophy type 3, 253400 to Spinal muscular atrophy type 1, MIM#253300
BabyScreen+ newborn screening v0.276 SMN1 Zornitza Stark reviewed gene: SMN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy-1, MIM# 253300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.276 GALE Zornitza Stark Marked gene: GALE as ready
BabyScreen+ newborn screening v0.276 GALK1 Zornitza Stark Marked gene: GALK1 as ready
BabyScreen+ newborn screening v0.276 GALK1 Zornitza Stark reviewed gene: GALK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Galactokinase deficiency with cataracts MIM#230200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.276 GALT Zornitza Stark Marked gene: GALT as ready
BabyScreen+ newborn screening v0.276 TAT Zornitza Stark Marked gene: TAT as ready
BabyScreen+ newborn screening v0.276 PCCB Zornitza Stark Marked gene: PCCB as ready
BabyScreen+ newborn screening v0.275 PCCA Zornitza Stark Marked gene: PCCA as ready
BabyScreen+ newborn screening v0.275 PCBD1 Zornitza Stark Marked gene: PCBD1 as ready
BabyScreen+ newborn screening v0.275 QDPR Zornitza Stark Marked gene: QDPR as ready
BabyScreen+ newborn screening v0.275 PTS Zornitza Stark Marked gene: PTS as ready
BabyScreen+ newborn screening v0.275 PAH Zornitza Stark Marked gene: PAH as ready
BabyScreen+ newborn screening v0.275 ETFB Zornitza Stark Marked gene: ETFB as ready
BabyScreen+ newborn screening v0.275 ETFB Zornitza Stark reviewed gene: ETFB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric acidemia IIB, MIM# 231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.275 ETFA Zornitza Stark Marked gene: ETFA as ready
BabyScreen+ newborn screening v0.274 ETFA Zornitza Stark changed review comment from: Well established gene-disease association.

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress.

Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates, D,L-3-hydroxybutyrate

Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis; to: Well established gene-disease association.

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress.

Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates, D,L-3-hydroxybutyrate (PMID 31904027)

Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis
BabyScreen+ newborn screening v0.274 ETFA Zornitza Stark reviewed gene: ETFA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric acidemia IIA, MIM# 231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 NOTCH3 David Amor reviewed gene: NOTCH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 (CADASIL); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.274 NOG David Amor reviewed gene: NOG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Brachydactyly, type B2, Multiple synostoses syndrome 1, Stapes ankylosis with broad thumbs and toes, Symphalangism, proximal, 1A, Tarsal-carpal coalition syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.274 NKX2-1 David Amor reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, NKX2-1-Related Disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.274 NHEJ1 David Amor reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 NEFL David Amor reviewed gene: NEFL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate G, Charcot-Marie-Tooth disease, type 1F, Charcot-Marie-Tooth disease, type 2E; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 NEB David Amor reviewed gene: NEB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 2, autosomal recessive, Arthrogryposis multiplex congenita 6; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 NAGLU David Amor reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIB; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 MYH9 David Amor reviewed gene: MYH9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 17, Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.274 MYH7 David Amor reviewed gene: MYH7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Various myopathies and cardiomyopathies; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 MYH3 David Amor reviewed gene: MYH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon) (AD), Arthrogryposis, distal, type 2B3 (Sheldon-Hall) (AD), Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B (AR); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 MYBPC1 David Amor reviewed gene: MYBPC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lethal congenital contracture syndrome 4 (AR), Arthrogryposis, distal, type 1B; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 MYSM1 David Amor reviewed gene: MYSM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bone marrow failure syndrome 4; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 MSX2 David Amor reviewed gene: MSX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis, parietal foramina; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.274 MTM1 David Amor edited their review of gene: MTM1: Changed phenotypes: X-linked myotubular myopathy
BabyScreen+ newborn screening v0.274 MPZ David Amor reviewed gene: MPZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: CMT1B (AD), Dejerine-Sottas disease (AR); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 MPL David Amor reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32703794; Phenotypes: Congenital amegakaryocytic thrombocytopenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 MLYCD David Amor reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Malonyl-CoA decarboxylase deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.274 ZIC3 Lilian Downie reviewed gene: ZIC3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29442328, PMID: 27406248; Phenotypes: X linked heterotaxy and congenital heart defects MIM:306955; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.274 ETFDH Zornitza Stark Marked gene: ETFDH as ready
BabyScreen+ newborn screening v0.274 ETFDH Zornitza Stark Phenotypes for gene: ETFDH were changed from Glutaric acidemia IIC, MIM#231680 to Glutaric acidemia IIC, MIM#231680
BabyScreen+ newborn screening v0.272 ETFDH Zornitza Stark reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 31904027; Phenotypes: Glutaric acidemia IIC, MIM# 231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.272 HADHB Zornitza Stark Marked gene: HADHB as ready
BabyScreen+ newborn screening v0.272 HADHA Zornitza Stark Marked gene: HADHA as ready
BabyScreen+ newborn screening v0.271 HADHA Zornitza Stark changed review comment from: Well established gene-disease association.

Clinical presentation is characterised by early-onset cardiomyopathy, hypoglycaemia, neuropathy, and pigmentary retinopathy, and sudden death

Treatment: IV glucose during acute episodes, avoid fasting, carnitine, restrict LCFA, bezafibrate, triheptanoin; to: Well established gene-disease association.

Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy.

Treatment: IV glucose during acute episodes, avoid fasting, carnitine, restrict LCFA, bezafibrate, triheptanoin
BabyScreen+ newborn screening v0.271 MMAA Zornitza Stark Marked gene: MMAA as ready
BabyScreen+ newborn screening v0.271 MUT Zornitza Stark Marked gene: MUT as ready
BabyScreen+ newborn screening v0.270 ACADM Zornitza Stark Marked gene: ACADM as ready
BabyScreen+ newborn screening v0.270 ZNF469 Lilian Downie changed review comment from: Well established gene-disease association.

Severe, causes blindness in the majority in early childhood but variable. Connective tissue disease spectrum. Can cause ocular rupture.

Treatment: lifestyle modification (rupture can occur from minor trauma), protective eyewear and avoidance of contact sports and activities, different surgical techniques have been tried in patients with variable success; to: Well established gene-disease association.

Severe, causes blindness in the majority in early childhood but variable. Corneal thinning. Connective tissue disease spectrum, can have systemic features. Ocular rupture causes blindness.

Treatment: lifestyle modification (rupture can occur from minor trauma), protective eyewear and avoidance of contact sports and activities, different surgical techniques have been tried in patients with variable success
BabyScreen+ newborn screening v0.270 ZNF469 Lilian Downie changed review comment from: Well established gene-disease association.

Severe, can cause blindness in early childhood but variable. Connective tissue disease spectrum. Can cause ocular rupture.

Treatment: no, only lifestyle modification (rupture can occur from minor trauma) and protective eyewear.; to: Well established gene-disease association.

Severe, causes blindness in the majority in early childhood but variable. Connective tissue disease spectrum. Can cause ocular rupture.

Treatment: lifestyle modification (rupture can occur from minor trauma), protective eyewear and avoidance of contact sports and activities, different surgical techniques have been tried in patients with variable success
BabyScreen+ newborn screening v0.270 LRP4 David Amor changed review comment from: Gene-disease association: strong but <1% of all CMS (very rare)

Onset:infancy or childhood

Treatment: Not clear that there is any treatment that helps, but early diagnosis may still be useful; to: Gene-disease association: strong but <1% of all CMS (very rare)

Onset:infancy or childhood

Treatment: Not clear that there is any treatment that helps, but early diagnosis may still be useful
BabyScreen+ newborn screening v0.270 LAMB3 David Amor changed review comment from: Gene-disease association: well established

Age of onset: congenital

Treatment: non specific but early detection may be beneficial; to: Gene-disease association: well established

Age of onset: congenital

Treatment: non specific but early detection may be beneficial
BabyScreen+ newborn screening v0.270 MITF David Amor reviewed gene: MITF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wardenburg syndrome type 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.270 MFN2 David Amor reviewed gene: MFN2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth Neuropathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.270 MEGF10 David Amor reviewed gene: MEGF10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.270 BTD Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity and age of presentation, predominantly with cutaneous and neurologic abnormalities

Treatment: biotin

Non-genetic confirmatory testing: biotinidase enzyme activity in serum or plasma; to: Well established gene-disease association.

Variable severity and age of presentation, predominantly with cutaneous and neurologic abnormalities. Phenotype can be difficult to predict from genotype, however note currently included in tNBS.

Treatment: biotin

Non-genetic confirmatory testing: biotinidase enzyme activity in serum or plasma
BabyScreen+ newborn screening v0.270 BTD Zornitza Stark Marked gene: BTD as ready
BabyScreen+ newborn screening v0.270 HLCS Zornitza Stark Marked gene: HLCS as ready
BabyScreen+ newborn screening v0.270 HLCS Zornitza Stark reviewed gene: HLCS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Holocarboxylase synthetase deficiency, MIM# 253270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.270 GCDH Zornitza Stark Marked gene: GCDH as ready
BabyScreen+ newborn screening v0.270 GCDH Zornitza Stark reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 33069577; Phenotypes: Glutaric aciduria, type I MIM#231670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.270 CBS Zornitza Stark changed review comment from: Well established gene-disease association.

Multi-system disorder, onset in infancy.
In general, individuals appear normal at birth but have a progressive disease course if untreated. Clinical features typically manifest in the first or second decade of life. Intellectual disability may be the first recognizable sign and may present as developmental delay after the first to second year of life. Myopia typically occurs after age one with the majority of untreated individuals developing ectopia lentis by age 8. Roughly half of patients show signs of osteoporosis by their teens. Cerebrovascular events typically manifest during young adulthood, though they have been reported earlier. Thromboembolism is the major cause of early death and morbidity. Among B₆-responsive individuals, a vascular event in adolescence or adulthood is often the presenting feature.

Treatment: vitamin B6 (pyridoxine), methionine-restricted diet, folate, vitamin B12, betaine. Management guidelines PMID 27778219.

Non-genetic confirmatory testing: plasma total homocysteine and plasma amino acids

Paediatric actionable gene by ClinGen.; to: Well established gene-disease association.

Multi-system disorder, onset in infancy.
In general, individuals appear normal at birth but have a progressive disease course if untreated. Clinical features typically manifest in the first or second decade of life. Intellectual disability may be the first recognizable sign and may present as developmental delay after the first to second year of life. Myopia typically occurs after age one with the majority of untreated individuals developing ectopia lentis by age 8. Roughly half of patients show signs of osteoporosis by their teens. Cerebrovascular events typically manifest during young adulthood, though they have been reported earlier. Thromboembolism is the major cause of early death and morbidity. Among B₆-responsive individuals, a vascular event in adolescence or adulthood is often the presenting feature.

Treatment: vitamin B6 (pyridoxine), methionine-restricted diet, folate, vitamin B12, betaine. Management guidelines PMID 27778219.

Non-genetic confirmatory testing: plasma total homocysteine and plasma amino acids

Paediatric actionable gene by ClinGen.

Note excluded from reproductive carrier screening tests due to poor mappability, for review.
BabyScreen+ newborn screening v0.270 CBS Zornitza Stark Marked gene: CBS as ready
BabyScreen+ newborn screening v0.268 CFTR Zornitza Stark Marked gene: CFTR as ready
BabyScreen+ newborn screening v0.268 CFTR Zornitza Stark changed review comment from: Well established gene-disease association.

Typically presents in infancy and early childhood.

Early treatment improves outcomes.

Non-genetic confirmatory testing available.; to: Well established gene-disease association.

Typically presents in infancy and early childhood.

Early treatment improves outcomes.

Non-genetic confirmatory testing available: sweat test.
BabyScreen+ newborn screening v0.268 CYP21A2 Zornitza Stark Marked gene: CYP21A2 as ready
BabyScreen+ newborn screening v0.268 MMADHC Zornitza Stark reviewed gene: MMADHC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Homocystinuria, cblD type, variant 1 MIM#277410, Methylmalonic aciduria and homocystinuria, cblD type MIM#277410, Methylmalonic aciduria, cblD type, variant 2 MIM#277410, Disorders of cobalamin absorption, transport and metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.268 MMACHC Zornitza Stark Marked gene: MMACHC as ready
BabyScreen+ newborn screening v0.268 SLC25A20 Zornitza Stark reviewed gene: SLC25A20: Rating: GREEN; Mode of pathogenicity: None; Publications: 33085788, 32885845; Phenotypes: Carnitine-acylcarnitine translocase deficiency, MIM# 212138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.268 SLC22A5 Zornitza Stark Marked gene: SLC22A5 as ready
BabyScreen+ newborn screening v0.268 SLC22A5 Zornitza Stark reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Carnitine deficiency, systemic primary, MIM# 212140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.268 MT-RNR1 Zornitza Stark Marked gene: MT-RNR1 as ready
BabyScreen+ newborn screening v0.267 MT-RNR1 Zornitza Stark gene: MT-RNR1 was added
gene: MT-RNR1 was added to gNBS. Sources: Expert Review
pharmacogenomic tags were added to gene: MT-RNR1.
Mode of inheritance for gene gene: MT-RNR1 was set to MITOCHONDRIAL
Phenotypes for gene: MT-RNR1 were set to Aminoglycoside sensitivity
Review for gene: MT-RNR1 was set to GREEN
Added comment: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G
m.1005T>C
m.1095T>C

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review
BabyScreen+ newborn screening v0.266 CHRND John Christodoulou changed review comment from: congenital myasthenia syndrome

anti cholinesterase inhibitors partially effective - PMID: 30808424; www.ncbi.nlm.nih.gov/books/NBK1168/#cms.Summary; to: congenital myasthenia syndrome

anti cholinesterase inhibitors partially effective; 3,4-DAP effective - PMID: 30808424; www.ncbi.nlm.nih.gov/books/NBK1168/#cms.Summary
BabyScreen+ newborn screening v0.265 MC2R Zornitza Stark Marked gene: MC2R as ready
BabyScreen+ newborn screening v0.265 MBTPS2 Zornitza Stark Marked gene: MBTPS2 as ready
BabyScreen+ newborn screening v0.265 MBTPS2 Zornitza Stark Phenotypes for gene: MBTPS2 were changed from Ichthyosis follicularis, alopecia & photophobia to IFAP syndrome with or without BRESHECK syndrome MIM#308205
BabyScreen+ newborn screening v0.263 MARVELD2 Zornitza Stark Marked gene: MARVELD2 as ready
BabyScreen+ newborn screening v0.263 MARVELD2 Zornitza Stark Gene: marveld2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.263 MARVELD2 Zornitza Stark Phenotypes for gene: MARVELD2 were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 49, MIM# 610153
BabyScreen+ newborn screening v0.262 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
BabyScreen+ newborn screening v0.262 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from Cardiofaciocutaneous syndrome to Cardiofaciocutaneous syndrome 4, MIM# 615280
BabyScreen+ newborn screening v0.260 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
BabyScreen+ newborn screening v0.260 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from Cardiofaciocutaneous syndrome to Cardiofaciocutaneous syndrome 3, MIM# 615279
BabyScreen+ newborn screening v0.258 MAN2B1 Zornitza Stark Marked gene: MAN2B1 as ready
BabyScreen+ newborn screening v0.257 MAFB Zornitza Stark Marked gene: MAFB as ready
BabyScreen+ newborn screening v0.257 MAFB Zornitza Stark Phenotypes for gene: MAFB were changed from Multicentric carpotarsal osteolysis syndrome to Multicentric carpotarsal osteolysis syndrome (MIM#166300)
BabyScreen+ newborn screening v0.255 MAFB Zornitza Stark reviewed gene: MAFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 33975323; Phenotypes: Multicentric carpotarsal osteolysis syndrome (MIM#166300); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.255 MAD2L2 Zornitza Stark Marked gene: MAD2L2 as ready
BabyScreen+ newborn screening v0.253 LTBP4 Zornitza Stark Marked gene: LTBP4 as ready
BabyScreen+ newborn screening v0.251 LRTOMT Zornitza Stark Marked gene: LRTOMT as ready
BabyScreen+ newborn screening v0.250 LRRC6 Zornitza Stark Marked gene: LRRC6 as ready
BabyScreen+ newborn screening v0.250 LRRC6 Zornitza Stark Phenotypes for gene: LRRC6 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 19, MIM# 614935
BabyScreen+ newborn screening v0.248 LRRC6 Zornitza Stark reviewed gene: LRRC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 19, MIM# 614935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.248 LRSAM1 Zornitza Stark Marked gene: LRSAM1 as ready
BabyScreen+ newborn screening v0.248 LRSAM1 Zornitza Stark Phenotypes for gene: LRSAM1 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, axonal, type 2P, MIM# 614436
BabyScreen+ newborn screening v0.245 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
BabyScreen+ newborn screening v0.245 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from Leigh syndrome to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111
BabyScreen+ newborn screening v0.243 LRPPRC Zornitza Stark reviewed gene: LRPPRC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.243 LRP5 Zornitza Stark Marked gene: LRP5 as ready
BabyScreen+ newborn screening v0.241 MCFD2 David Amor changed review comment from: Gene-disease association: strong but rare.

Onset: birth

Treatment: clotting factor supplementation, However only reported to cause mild-moderate bleeding tendency so consider excluding?; to: Gene-disease association: strong but rare.

Onset: birth

Treatment: clotting factor supplementation, However only reported to cause mild-moderate bleeding tendency so consider excluding?
BabyScreen+ newborn screening v0.241 LRP4 Zornitza Stark Marked gene: LRP4 as ready
BabyScreen+ newborn screening v0.240 LRP2 Zornitza Stark Marked gene: LRP2 as ready
BabyScreen+ newborn screening v0.240 LRP2 Zornitza Stark Phenotypes for gene: LRP2 were changed from Donnai-Barrow syndrome to Donnai-Barrow syndrome, MIM#222448
BabyScreen+ newborn screening v0.238 LRP2 Zornitza Stark reviewed gene: LRP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Donnai-Barrow syndrome, MIM#222448; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.238 LOXHD1 Zornitza Stark Marked gene: LOXHD1 as ready
BabyScreen+ newborn screening v0.237 LMX1B Zornitza Stark Marked gene: LMX1B as ready
BabyScreen+ newborn screening v0.235 LMOD3 Zornitza Stark Marked gene: LMOD3 as ready
BabyScreen+ newborn screening v0.233 LMBRD1 Zornitza Stark Marked gene: LMBRD1 as ready
BabyScreen+ newborn screening v0.233 LITAF Zornitza Stark Marked gene: LITAF as ready
BabyScreen+ newborn screening v0.233 LITAF Zornitza Stark Phenotypes for gene: LITAF were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 1C, MIM# 601098
BabyScreen+ newborn screening v0.230 LIPA Zornitza Stark Marked gene: LIPA as ready
BabyScreen+ newborn screening v0.229 LIG4 Zornitza Stark Marked gene: LIG4 as ready
BabyScreen+ newborn screening v0.229 MBTPS2 David Amor reviewed gene: MBTPS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: IFAP syndrome: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.229 MARVELD2 David Amor reviewed gene: MARVELD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-syndromic deafness, prelingual; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.229 MAFB David Amor reviewed gene: MAFB: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: Multicentric carpotarsal osteolysis syndrome, renal failure; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.228 LIFR Zornitza Stark Marked gene: LIFR as ready
BabyScreen+ newborn screening v0.228 LIFR Zornitza Stark Phenotypes for gene: LIFR were changed from Stuve-Wiedemann syndrome to Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, MIM# 601559
BabyScreen+ newborn screening v0.227 LIFR Zornitza Stark edited their review of gene: LIFR: Changed phenotypes: Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, MIM# 601559
BabyScreen+ newborn screening v0.226 LHX4 Zornitza Stark Marked gene: LHX4 as ready
BabyScreen+ newborn screening v0.225 LHX4 Zornitza Stark reviewed gene: LHX4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 4, MIM# 262700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.225 LHX3 Zornitza Stark Marked gene: LHX3 as ready
BabyScreen+ newborn screening v0.225 LHX3 Zornitza Stark reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM#221750); Mode of inheritance: None
BabyScreen+ newborn screening v0.225 LHFPL5 Zornitza Stark Marked gene: LHFPL5 as ready
BabyScreen+ newborn screening v0.224 LEPR Zornitza Stark Marked gene: LEPR as ready
BabyScreen+ newborn screening v0.222 LDLR Zornitza Stark changed review comment from: ClinGen: 'strong actionability' in paediatric patients.

For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.; to: ClinGen: 'strong actionability' in paediatric patients.

For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.
BabyScreen+ newborn screening v0.222 LARS2 Zornitza Stark changed review comment from: For review. Treatment is supportive.; to: For review. Variable severity. Treatment is supportive.
BabyScreen+ newborn screening v0.222 LARS2 Zornitza Stark Marked gene: LARS2 as ready
BabyScreen+ newborn screening v0.222 LARS2 Zornitza Stark Gene: lars2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.222 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from Perrault syndrome to Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Perrault syndrome 4, MIM# 615300
BabyScreen+ newborn screening v0.221 LARS2 Zornitza Stark Classified gene: LARS2 as Red List (low evidence)
BabyScreen+ newborn screening v0.221 LARS2 Zornitza Stark Gene: lars2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.220 LARS2 Zornitza Stark reviewed gene: LARS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.220 LDLR Zornitza Stark Marked gene: LDLR as ready
BabyScreen+ newborn screening v0.218 LARGE1 Zornitza Stark Marked gene: LARGE1 as ready
BabyScreen+ newborn screening v0.218 LARGE1 Zornitza Stark Gene: large1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.218 LARGE1 Zornitza Stark Phenotypes for gene: LARGE1 were changed from Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840
BabyScreen+ newborn screening v0.217 LARGE1 Zornitza Stark Classified gene: LARGE1 as Red List (low evidence)
BabyScreen+ newborn screening v0.217 LARGE1 Zornitza Stark Gene: large1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.216 LARGE1 Zornitza Stark reviewed gene: LARGE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.216 LAMTOR2 Zornitza Stark Marked gene: LAMTOR2 as ready
BabyScreen+ newborn screening v0.214 LAMP2 Zornitza Stark Marked gene: LAMP2 as ready
BabyScreen+ newborn screening v0.211 LAMC2 Zornitza Stark Marked gene: LAMC2 as ready
BabyScreen+ newborn screening v0.209 LAMB2 Zornitza Stark Marked gene: LAMB2 as ready
BabyScreen+ newborn screening v0.209 LAMB2 Zornitza Stark Phenotypes for gene: LAMB2 were changed from Pierson syndrome to Nephrotic syndrome, type 5, with or without ocular abnormalities, MIM# 614199; Pierson syndrome, MIM# 609049
BabyScreen+ newborn screening v0.207 LAMB2 Zornitza Stark reviewed gene: LAMB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrotic syndrome, type 5, with or without ocular abnormalities, MIM# 614199, Pierson syndrome, MIM# 609049; Mode of inheritance: None
BabyScreen+ newborn screening v0.207 LAMA3 Zornitza Stark Marked gene: LAMA3 as ready
BabyScreen+ newborn screening v0.205 LAMA2 Zornitza Stark reviewed gene: LAMA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.205 ARSB John Christodoulou reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.205 ARG1 John Christodoulou reviewed gene: ARG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.205 LRRC6 David Amor reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.205 CPT2 Zornitza Stark Marked gene: CPT2 as ready
BabyScreen+ newborn screening v0.205 CPT2 Zornitza Stark Phenotypes for gene: CPT2 were changed from Carnitine palmitoyltransferase 2 deficiency to CPT II deficiency, infantile 600649; CPT II deficiency, lethal neonatal 608836; CPT II deficiency, myopathic, stress-induced 255110
BabyScreen+ newborn screening v0.203 CPT1A Zornitza Stark Marked gene: CPT1A as ready
BabyScreen+ newborn screening v0.202 LRP2 David Amor reviewed gene: LRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Donnai-Barrow syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.202 BCKDHB Zornitza Stark Marked gene: BCKDHB as ready
BabyScreen+ newborn screening v0.201 BCKDHA Zornitza Stark Marked gene: BCKDHA as ready
BabyScreen+ newborn screening v0.200 DBT Zornitza Stark Marked gene: DBT as ready
BabyScreen+ newborn screening v0.200 LITAF David Amor reviewed gene: LITAF: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: CMT1C; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.200 ASS1 Zornitza Stark Marked gene: ASS1 as ready
BabyScreen+ newborn screening v0.199 ACAT1 Zornitza Stark Marked gene: ACAT1 as ready
BabyScreen+ newborn screening v0.199 HMGCL Zornitza Stark Marked gene: HMGCL as ready
BabyScreen+ newborn screening v0.199 LHX4 David Amor reviewed gene: LHX4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: combined pituitary hormone deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.199 LHX3 David Amor reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency; Mode of inheritance: None
BabyScreen+ newborn screening v0.199 LEPR David Amor reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: severe early onset obesity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.199 LARS2 David Amor reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Perrault syndrome, sensorineural hearing loss, ovarian dysfunction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.199 LARGE1 David Amor reviewed gene: LARGE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wlaker-Warburg syndrome, muscular dystrophy-dystroglycanopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.199 LAMP2 David Amor reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Danon disease - cardiomyopathy, retinal disease, cognitive dysfunction; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.199 LAMA2 David Amor reviewed gene: LAMA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: LAMA2 muscular dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.199 GALT John Christodoulou commented on gene: GALT: part of newborn screening programs nationally (but not in Victoria)
BabyScreen+ newborn screening v0.198 BRAF Zornitza Stark Marked gene: BRAF as ready
BabyScreen+ newborn screening v0.197 BRAF Zornitza Stark reviewed gene: BRAF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 7, MIM# 613706, Cardiofaciocutaneous syndrome, MIM# 115150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.197 BIN1 Zornitza Stark Marked gene: BIN1 as ready
BabyScreen+ newborn screening v0.197 BIN1 Zornitza Stark Phenotypes for gene: BIN1 were changed from Myopathy, centronuclear, autosomal recessive to Centronuclear myopathy 2, MIM# 255200
BabyScreen+ newborn screening v0.195 BIN1 Zornitza Stark reviewed gene: BIN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Centronuclear myopathy 2, MIM# 255200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.195 BICD2 Zornitza Stark Marked gene: BICD2 as ready
BabyScreen+ newborn screening v0.195 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from Congenital spinal muscular atrophy to Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291; Neurodevelopmental disorder (MONDO#0700092), BICD2-related
BabyScreen+ newborn screening v0.191 BICD2 Zornitza Stark reviewed gene: BICD2: Rating: RED; Mode of pathogenicity: None; Publications: 23664116, 23664119, 23664120, 27751653, 28635954, 30054298, 29528393, 35896821; Phenotypes: Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290, MONDO:0014121, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291, Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.191 ATP6V1B1 Zornitza Stark Marked gene: ATP6V1B1 as ready
BabyScreen+ newborn screening v0.191 ATP6V1B1 Zornitza Stark Phenotypes for gene: ATP6V1B1 were changed from Renal tubular acidosis & hearing loss, MIM#267300 to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300
BabyScreen+ newborn screening v0.190 ATP8B1 Zornitza Stark Marked gene: ATP8B1 as ready
BabyScreen+ newborn screening v0.188 ACVRL1 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable age of symptom onset and severity.

No specific treatment available.; to: Well established gene-disease association.

Variable age of symptom onset and severity.

No specific treatment available.

However, management guidelines suggest screening in asymptomatic children for pulmonary AVMs, PMID 32894695.
BabyScreen+ newborn screening v0.188 ACVRL1 Zornitza Stark Marked gene: ACVRL1 as ready
BabyScreen+ newborn screening v0.187 ACVRL1 Zornitza Stark reviewed gene: ACVRL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.187 ATP6V0A4 Zornitza Stark Marked gene: ATP6V0A4 as ready
BabyScreen+ newborn screening v0.187 ACVR1 Zornitza Stark Marked gene: ACVR1 as ready
BabyScreen+ newborn screening v0.184 ACOX1 Zornitza Stark Marked gene: ACOX1 as ready
BabyScreen+ newborn screening v0.180 ALDOB Zornitza Stark Marked gene: ALDOB as ready
BabyScreen+ newborn screening v0.180 ALDOB Zornitza Stark Phenotypes for gene: ALDOB were changed from Fructose intolerance, MIM#229600 to Fructose intolerance, hereditary, MIM# 229600
BabyScreen+ newborn screening v0.179 ALDOB Zornitza Stark edited their review of gene: ALDOB: Changed phenotypes: Fructose intolerance, hereditary, MIM# 229600
BabyScreen+ newborn screening v0.179 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
BabyScreen+ newborn screening v0.177 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
BabyScreen+ newborn screening v0.173 ALG9 Zornitza Stark Marked gene: ALG9 as ready
BabyScreen+ newborn screening v0.171 ALG8 Zornitza Stark Marked gene: ALG8 as ready
BabyScreen+ newborn screening v0.169 ALG6 Zornitza Stark Marked gene: ALG6 as ready
BabyScreen+ newborn screening v0.167 ALG3 Zornitza Stark Marked gene: ALG3 as ready
BabyScreen+ newborn screening v0.165 ALG12 Zornitza Stark Marked gene: ALG12 as ready
BabyScreen+ newborn screening v0.163 ALG1 Zornitza Stark Marked gene: ALG1 as ready
BabyScreen+ newborn screening v0.161 ATP7A Zornitza Stark changed review comment from: Well established gene-disease association.

ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.

Menkes disease typically presents in infancy, and if untreated is fatal. Typical age at diagnosis is ~8 months.

Females are typically asymptomatic.

In Australia, the birth incidence of MD is reported to be much higher (1/40,000-100,000 cf 1 in 300,000 elsewhere), which may be due to a founder effect

Treatment: subcutaneous injections of copper histidine or copper chloride

ClinGen has assessed as moderate evidence for actionability.

Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms.; to: Well established gene-disease association.

ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.

Menkes disease typically presents in infancy, and if untreated is fatal. Typical age at diagnosis is ~8 months.

Females are typically asymptomatic.

In Australia, the birth incidence of MD is reported to be much higher (1/40,000-100,000 cf 1 in 300,000 elsewhere), which may be due to a founder effect.

Non-genetic confirmatory testing: serum ceruloplasmin and copper, plasma catechols

Treatment: subcutaneous injections of copper histidine or copper chloride

ClinGen has assessed as moderate evidence for actionability.

Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms.
BabyScreen+ newborn screening v0.161 ATP7A Zornitza Stark Marked gene: ATP7A as ready
BabyScreen+ newborn screening v0.160 ATRX Zornitza Stark Marked gene: ATRX as ready
BabyScreen+ newborn screening v0.160 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580
BabyScreen+ newborn screening v0.158 ATRX Zornitza Stark reviewed gene: ATRX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha-thalassemia/mental retardation syndrome, MIM# 301040, Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.158 BAAT Zornitza Stark Marked gene: BAAT as ready
BabyScreen+ newborn screening v0.156 B3GLCT Zornitza Stark Marked gene: B3GLCT as ready
BabyScreen+ newborn screening v0.154 BBS9 Zornitza Stark Marked gene: BBS9 as ready
BabyScreen+ newborn screening v0.154 BBS9 Zornitza Stark Phenotypes for gene: BBS9 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 9, MIM#615986
BabyScreen+ newborn screening v0.152 BBS9 Zornitza Stark reviewed gene: BBS9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 9, MIM#615986; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.152 BBS7 Zornitza Stark Marked gene: BBS7 as ready
BabyScreen+ newborn screening v0.152 BBS7 Zornitza Stark Phenotypes for gene: BBS7 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 7, MIM# 615984
BabyScreen+ newborn screening v0.150 BBS7 Zornitza Stark reviewed gene: BBS7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 7, MIM# 615984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.150 BBS5 Zornitza Stark Marked gene: BBS5 as ready
BabyScreen+ newborn screening v0.150 BBS5 Zornitza Stark Phenotypes for gene: BBS5 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 5, MIM#615983
BabyScreen+ newborn screening v0.148 BBS5 Zornitza Stark reviewed gene: BBS5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 5, MIM#615983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.148 BBS4 Zornitza Stark Marked gene: BBS4 as ready
BabyScreen+ newborn screening v0.148 BBS4 Zornitza Stark Phenotypes for gene: BBS4 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 4, MIM#615982
BabyScreen+ newborn screening v0.146 BBS4 Zornitza Stark reviewed gene: BBS4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 4, MIM#615982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.146 BBS2 Zornitza Stark Marked gene: BBS2 as ready
BabyScreen+ newborn screening v0.146 BBS2 Zornitza Stark Phenotypes for gene: BBS2 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 2, MIM# 615981
BabyScreen+ newborn screening v0.144 BBS2 Zornitza Stark reviewed gene: BBS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 2, MIM# 615981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.144 BBS12 Zornitza Stark Marked gene: BBS12 as ready
BabyScreen+ newborn screening v0.144 BBS12 Zornitza Stark Phenotypes for gene: BBS12 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 12, MIM# 615989
BabyScreen+ newborn screening v0.142 BBS12 Zornitza Stark reviewed gene: BBS12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 12, MIM# 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.142 BBS10 Zornitza Stark Marked gene: BBS10 as ready
BabyScreen+ newborn screening v0.142 BBS10 Zornitza Stark Phenotypes for gene: BBS10 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 10, MIM# 615987
BabyScreen+ newborn screening v0.140 BBS10 Zornitza Stark reviewed gene: BBS10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 10, MIM# 615987; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.140 BBS1 Zornitza Stark Marked gene: BBS1 as ready
BabyScreen+ newborn screening v0.140 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 1, MIM# 209900
BabyScreen+ newborn screening v0.138 BBS1 Zornitza Stark reviewed gene: BBS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 1, MIM# 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.138 ATP6V1B1 Zornitza Stark reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.138 ATP6V0A4 Zornitza Stark reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal tubular acidosis, distal, autosomal recessive, MIM#602722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.138 ATP6V0A2 Zornitza Stark Marked gene: ATP6V0A2 as ready
BabyScreen+ newborn screening v0.136 ATP2A1 Zornitza Stark Marked gene: ATP2A1 as ready
BabyScreen+ newborn screening v0.134 ATM Zornitza Stark Marked gene: ATM as ready
BabyScreen+ newborn screening v0.132 ASPA Zornitza Stark Marked gene: ASPA as ready
BabyScreen+ newborn screening v0.130 ARPC1B Zornitza Stark Marked gene: ARPC1B as ready
BabyScreen+ newborn screening v0.130 ARPC1B Zornitza Stark Gene: arpc1b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.130 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
BabyScreen+ newborn screening v0.128 ARX Zornitza Stark Marked gene: ARX as ready
BabyScreen+ newborn screening v0.128 ARX Zornitza Stark Gene: arx has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.128 ARX Zornitza Stark Phenotypes for gene: ARX were changed from Lissencephaly, X-linked 2 to Lissencephaly, X-linked 2, MIM# 300215
BabyScreen+ newborn screening v0.127 ARX Zornitza Stark Classified gene: ARX as Red List (low evidence)
BabyScreen+ newborn screening v0.127 ARX Zornitza Stark Gene: arx has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.126 ARX Zornitza Stark reviewed gene: ARX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly, X-linked 2, MIM# 300215; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.126 ARSA Zornitza Stark Marked gene: ARSA as ready
BabyScreen+ newborn screening v0.126 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.126 ARSA Zornitza Stark Phenotypes for gene: ARSA were changed from Metachromatic leukodystrophy to Metachromatic leukodystrophy, MIM# 250100
BabyScreen+ newborn screening v0.125 ARSA Zornitza Stark Tag for review tag was added to gene: ARSA.
Tag treatable tag was added to gene: ARSA.
Tag clinical trial tag was added to gene: ARSA.
BabyScreen+ newborn screening v0.125 ARSA Zornitza Stark reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Metachromatic leukodystrophy, MIM# 250100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.125 ARPC1B Zornitza Stark changed review comment from: Established gene-disease association, 3 families and functional data.

Severe disorder with onset in infancy/childhood. Recurrent infections and inflammatory features such as vasculitis and eczema.

Treatable: bone marrow transplant.; to: Established gene-disease association, 9 families and functional data.

Severe disorder with onset in infancy/childhood. Recurrent infections and inflammatory features such as vasculitis and eczema.

Treatable: bone marrow transplant.
BabyScreen+ newborn screening v0.125 ARPC1B Zornitza Stark Tag treatable tag was added to gene: ARPC1B.
BabyScreen+ newborn screening v0.125 ARPC1B Zornitza Stark reviewed gene: ARPC1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28368018, 33679784; Phenotypes: Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, MIM# 617718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.125 ARMC4 Zornitza Stark Marked gene: ARMC4 as ready
BabyScreen+ newborn screening v0.125 ARMC4 Zornitza Stark Gene: armc4 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.125 ARMC4 Zornitza Stark Phenotypes for gene: ARMC4 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 23, MIM# 615451
BabyScreen+ newborn screening v0.124 ARMC4 Zornitza Stark Classified gene: ARMC4 as Red List (low evidence)
BabyScreen+ newborn screening v0.124 ARMC4 Zornitza Stark Gene: armc4 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.123 ARMC4 Zornitza Stark reviewed gene: ARMC4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 23, MIM# 615451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.123 ARFGEF2 Zornitza Stark Marked gene: ARFGEF2 as ready
BabyScreen+ newborn screening v0.123 ARFGEF2 Zornitza Stark Gene: arfgef2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.123 ARFGEF2 Zornitza Stark Phenotypes for gene: ARFGEF2 were changed from Periventricular heterotopia with microcephaly to Periventricular heterotopia with microcephaly (MIM#608097)
BabyScreen+ newborn screening v0.122 ARFGEF2 Zornitza Stark Classified gene: ARFGEF2 as Red List (low evidence)
BabyScreen+ newborn screening v0.122 ARFGEF2 Zornitza Stark Gene: arfgef2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.121 ARFGEF2 Zornitza Stark reviewed gene: ARFGEF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Periventricular heterotopia with microcephaly (MIM#608097); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.121 AR Zornitza Stark Marked gene: AR as ready
BabyScreen+ newborn screening v0.121 AR Zornitza Stark Gene: ar has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.121 AR Zornitza Stark Phenotypes for gene: AR were changed from Androgen insensitivity, MIM# 300068 to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300
BabyScreen+ newborn screening v0.120 AR Zornitza Stark Classified gene: AR as Red List (low evidence)
BabyScreen+ newborn screening v0.120 AR Zornitza Stark Gene: ar has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.119 AR Zornitza Stark reviewed gene: AR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.119 AVPR2 Zornitza Stark changed review comment from: Well established gene-disease association.

Onset in infancy. Causes severe dehydration, can be life-threatening.

Treatment: hydration, low-salt, low-protein diet, thiazide diuretics, amiloride, indomethacin.

Clinical trials.; to: Well established gene-disease association.

Onset in infancy. Causes severe dehydration, can be life-threatening.

Treatment: hydration, low-salt, low-protein diet, thiazide diuretics, amiloride, indomethacin.

Clinical trials.

Around 10% of variants are large deletions.
BabyScreen+ newborn screening v0.119 AVP Zornitza Stark Marked gene: AVP as ready
BabyScreen+ newborn screening v0.117 AVPR2 Zornitza Stark Marked gene: AVPR2 as ready
BabyScreen+ newborn screening v0.117 AQP2 Zornitza Stark Marked gene: AQP2 as ready
BabyScreen+ newborn screening v0.116 APTX Zornitza Stark Marked gene: APTX as ready
BabyScreen+ newborn screening v0.116 APTX Zornitza Stark Phenotypes for gene: APTX were changed from Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia to Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia MIM#208920
BabyScreen+ newborn screening v0.113 APTX Zornitza Stark reviewed gene: APTX: Rating: RED; Mode of pathogenicity: None; Publications: 30986824, 26256098, 11586299; Phenotypes: Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia MIM#208920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.113 APRT Zornitza Stark Marked gene: APRT as ready
BabyScreen+ newborn screening v0.112 APOB Zornitza Stark Marked gene: APOB as ready
BabyScreen+ newborn screening v0.107 ARID1B Zornitza Stark Marked gene: ARID1B as ready
BabyScreen+ newborn screening v0.107 ARID1B Zornitza Stark Gene: arid1b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.107 ARID1B Zornitza Stark Phenotypes for gene: ARID1B were changed from Coffin-Siris syndrome to Coffin-Siris syndrome 1 MIM#135900
BabyScreen+ newborn screening v0.106 ARID1B Zornitza Stark Classified gene: ARID1B as Red List (low evidence)
BabyScreen+ newborn screening v0.106 ARID1B Zornitza Stark Gene: arid1b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.105 ARID1B Zornitza Stark reviewed gene: ARID1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome 1 MIM#135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.105 APC Zornitza Stark Marked gene: APC as ready
BabyScreen+ newborn screening v0.103 AP4M1 Zornitza Stark Marked gene: AP4M1 as ready
BabyScreen+ newborn screening v0.102 AP4M1 Zornitza Stark reviewed gene: AP4M1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 50, autosomal recessive, MIM# 612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.102 AP4E1 Zornitza Stark Marked gene: AP4E1 as ready
BabyScreen+ newborn screening v0.101 AP4E1 Zornitza Stark reviewed gene: AP4E1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 51, autosomal recessive, MIM# 613744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.101 AP4B1 Zornitza Stark Marked gene: AP4B1 as ready
BabyScreen+ newborn screening v0.100 AP4B1 Zornitza Stark reviewed gene: AP4B1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 47, autosomal recessive, MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.100 AP3B1 Zornitza Stark Marked gene: AP3B1 as ready
BabyScreen+ newborn screening v0.97 ANTXR2 Zornitza Stark Marked gene: ANTXR2 as ready
BabyScreen+ newborn screening v0.95 ANO10 Zornitza Stark Marked gene: ANO10 as ready
BabyScreen+ newborn screening v0.95 ANO10 Zornitza Stark Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10 to Spinocerebellar ataxia, autosomal recessive 10, MIM#613728
BabyScreen+ newborn screening v0.93 ANO10 Zornitza Stark reviewed gene: ANO10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia, autosomal recessive 10, MIM#613728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.93 ANKRD26 Zornitza Stark Marked gene: ANKRD26 as ready
BabyScreen+ newborn screening v0.91 ANKH Zornitza Stark Marked gene: ANKH as ready
BabyScreen+ newborn screening v0.89 ANK2 Zornitza Stark Marked gene: ANK2 as ready
BabyScreen+ newborn screening v0.88 ANK1 Zornitza Stark Marked gene: ANK1 as ready
BabyScreen+ newborn screening v0.85 AMT Zornitza Stark Marked gene: AMT as ready
BabyScreen+ newborn screening v0.83 AMN Zornitza Stark Marked gene: AMN as ready
BabyScreen+ newborn screening v0.83 AMN Zornitza Stark changed review comment from: Well established gene-disease association.

Imerslund-Grasbeck syndrome-2 (IGS2) is an autosomal recessive disorder characterized by onset of megaloblastic anaemia associated with decreased serum vitamin B12 (cobalamin, Cbl) in infancy or early childhood.; to: Well established gene-disease association.

Imerslund-Grasbeck syndrome-2 (IGS2) is an autosomal recessive disorder characterized by onset of megaloblastic anaemia associated with decreased serum vitamin B12 (cobalamin, Cbl) in infancy or early childhood.

Clinical features include failure to thrive, loss of appetite, fatigue, lethargy, and/or recurrent infections.

Treatment: cobalamin.
BabyScreen+ newborn screening v0.83 ALPL Zornitza Stark Marked gene: ALPL as ready
BabyScreen+ newborn screening v0.81 AMELX Zornitza Stark Marked gene: AMELX as ready
BabyScreen+ newborn screening v0.79 ALX4 Zornitza Stark Marked gene: ALX4 as ready
BabyScreen+ newborn screening v0.79 ALX4 Zornitza Stark Phenotypes for gene: ALX4 were changed from Parietal foramina 2 to Frontonasal dysplasia 2 MIM# 613451; Parietal foramina 2 MIM# 609597; {Craniosynostosis 5, susceptibility to} MIM#615529
BabyScreen+ newborn screening v0.76 ALX4 Zornitza Stark reviewed gene: ALX4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Frontonasal dysplasia 2 MIM# 613451, Parietal foramina 2 MIM# 609597, {Craniosynostosis 5, susceptibility to} MIM#615529; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.76 ALOXE3 Zornitza Stark Marked gene: ALOXE3 as ready
BabyScreen+ newborn screening v0.74 ALS2 Zornitza Stark Marked gene: ALS2 as ready
BabyScreen+ newborn screening v0.74 ALS2 Zornitza Stark Phenotypes for gene: ALS2 were changed from Amyotrophic lateral sclerosis to Infantile onset ascending spastic paralysis (MIM#607225); Juvenile amyotrophic lateral sclerosis 2 (MIM#205100); Juvenile primary lateral sclerosis (MIM#606353)
BabyScreen+ newborn screening v0.72 ALS2 Zornitza Stark reviewed gene: ALS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile onset ascending spastic paralysis (MIM#607225), Juvenile amyotrophic lateral sclerosis 2 (MIM#205100), Juvenile primary lateral sclerosis (MIM#606353); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.72 ALOX12B Zornitza Stark Marked gene: ALOX12B as ready
BabyScreen+ newborn screening v0.70 ALG14 Zornitza Stark Marked gene: ALG14 as ready
BabyScreen+ newborn screening v0.70 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates, MIM#616227 to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
BabyScreen+ newborn screening v0.68 ALG14 Zornitza Stark reviewed gene: ALG14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036, Disorder of N-glycosylation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.68 AKR1D1 Zornitza Stark Marked gene: AKR1D1 as ready
BabyScreen+ newborn screening v0.68 AK2 Zornitza Stark Marked gene: AK2 as ready
BabyScreen+ newborn screening v0.68 ADGRG1 Zornitza Stark Marked gene: ADGRG1 as ready
BabyScreen+ newborn screening v0.68 ADGRG1 Zornitza Stark Phenotypes for gene: ADGRG1 were changed from Polymicrogyria, bilateral frontoparietal to Polymicrogyria, bilateral frontoparietal, MIM#606854
BabyScreen+ newborn screening v0.66 ADGRG1 Zornitza Stark reviewed gene: ADGRG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Polymicrogyria, bilateral frontoparietal, MIM#606854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.65 ADAMTS13 Zornitza Stark Marked gene: ADAMTS13 as ready
BabyScreen+ newborn screening v0.65 ADAMTS13 Zornitza Stark reviewed gene: ADAMTS13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombotic thrombocytopenic purpura, hereditary, MIM# 274150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.65 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, MIM# 267500 to Reticular dysgenesis, MIM# 267500; MONDO:0009973
BabyScreen+ newborn screening v0.63 AK2 Zornitza Stark reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416, 19043417; Phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.63 AGRN Zornitza Stark Marked gene: AGRN as ready
BabyScreen+ newborn screening v0.62 ADA Zornitza Stark Marked gene: ADA as ready
BabyScreen+ newborn screening v0.60 ACTN1 Zornitza Stark Marked gene: ACTN1 as ready
BabyScreen+ newborn screening v0.58 ABCG5 Zornitza Stark Marked gene: ABCG5 as ready
BabyScreen+ newborn screening v0.57 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
BabyScreen+ newborn screening v0.56 ABCC6 Zornitza Stark Marked gene: ABCC6 as ready
BabyScreen+ newborn screening v0.56 ABCC6 Zornitza Stark changed review comment from: Well established gene-disease association.

Severe disorder with onset in infancy, can be fatal.

Treatment available: etidronate.; to: Well established gene-disease association.

Severe disorder with onset in infancy, can be fatal.

Treatment available: etidronate.

However, note excluded by other screening programs as severity difficult to predict from genotype and gene is also associated with PXE, a milder disorder.

There are also technical concerns due to 2x pseudogenes which cause mapping/variant calling issues in exons 1-9.
BabyScreen+ newborn screening v0.55 ABCC6 Zornitza Stark reviewed gene: ABCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 33005041, 34355424; Phenotypes: Arterial calcification, generalized, of infancy, 2, MIM# 614473; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.55 ABCC2 Zornitza Stark Marked gene: ABCC2 as ready
BabyScreen+ newborn screening v0.54 ABCB4 Zornitza Stark Marked gene: ABCB4 as ready
BabyScreen+ newborn screening v0.51 ABCB11 Zornitza Stark Marked gene: ABCB11 as ready
BabyScreen+ newborn screening v0.49 ABCA4 Zornitza Stark Marked gene: ABCA4 as ready
BabyScreen+ newborn screening v0.49 ABCA4 Zornitza Stark Phenotypes for gene: ABCA4 were changed from Stargardt disease to Cone-rod dystrophy 3, 604116; Fundus flavimaculatus, 248200; Retinal dystrophy, early-onset severe, 248200; Retinitis pigmentosa 19, 601718; Stargardt disease 1, 248200
BabyScreen+ newborn screening v0.47 ABCA4 Zornitza Stark reviewed gene: ABCA4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 3, 604116, Fundus flavimaculatus, 248200, Retinal dystrophy, early-onset severe, 248200, Retinitis pigmentosa 19, 601718, Stargardt disease 1, 248200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.47 ABCA3 Zornitza Stark Marked gene: ABCA3 as ready
BabyScreen+ newborn screening v0.47 ABCA3 Zornitza Stark Phenotypes for gene: ABCA3 were changed from Surfactant metabolism dysfunction, pulmonary, 3 to Surfactant metabolism dysfunction, pulmonary, 3, MIM# 610921
BabyScreen+ newborn screening v0.45 ABCA3 Zornitza Stark reviewed gene: ABCA3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 3, MIM# 610921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.45 ABCA12 Zornitza Stark Marked gene: ABCA12 as ready
BabyScreen+ newborn screening v0.45 ABCA12 Zornitza Stark Phenotypes for gene: ABCA12 were changed from Ichthyosis, congenital, autosomal recessive to Ichthyosis, congenital, autosomal recessive 4A (MIM#601277); Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500)
BabyScreen+ newborn screening v0.43 ABCA12 Zornitza Stark reviewed gene: ABCA12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 4A (MIM#601277), Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.43 AARS Zornitza Stark Marked gene: AARS as ready
BabyScreen+ newborn screening v0.43 AARS Zornitza Stark Gene: aars has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.43 AARS Zornitza Stark Phenotypes for gene: AARS were changed from Charcot-Marie-Tooth disease to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287
BabyScreen+ newborn screening v0.42 AARS Zornitza Stark Mode of inheritance for gene: AARS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.41 AARS Zornitza Stark Classified gene: AARS as Red List (low evidence)
BabyScreen+ newborn screening v0.41 AARS Zornitza Stark Gene: aars has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.40 AARS Zornitza Stark reviewed gene: AARS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 29, MIM# 616339, Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.40 AAAS Zornitza Stark Marked gene: AAAS as ready
BabyScreen+ newborn screening v0.38 ALDH7A1 Zornitza Stark Marked gene: ALDH7A1 as ready
BabyScreen+ newborn screening v0.37 ALDH5A1 Zornitza Stark Marked gene: ALDH5A1 as ready
BabyScreen+ newborn screening v0.35 ALDH3A2 Zornitza Stark Marked gene: ALDH3A2 as ready
BabyScreen+ newborn screening v0.35 ALDH3A2 Zornitza Stark Phenotypes for gene: ALDH3A2 were changed from Sjogren-Larsson syndrome to Sjogren-Larsson syndrome MIM#270200
BabyScreen+ newborn screening v0.33 ALDH3A2 Zornitza Stark reviewed gene: ALDH3A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Sjogren-Larsson syndrome MIM#270200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.33 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready