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| Fetal anomalies v1.254 | PSMF1 |
Zornitza Stark gene: PSMF1 was added gene: PSMF1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1 Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related Review for gene: PSMF1 was set to GREEN Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data. Sources: Literature |
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| Fetal anomalies v1.231 | FILIP1 | Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to ANeuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.216 | RBFOX2 |
Ain Roesley gene: RBFOX2 was added gene: RBFOX2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492; 37165897 Review for gene: RBFOX2 was set to AMBER gene: RBFOX2 was marked as current diagnostic Added comment: PMID: 37165897 1x 'splice altering' de novo in in an individual with HLSH + AVSD - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs). - PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492. - PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing. - PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS. - PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS. Sources: Literature |
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| Fetal anomalies v1.201 | CELSR3 |
Zornitza Stark gene: CELSR3 was added gene: CELSR3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CELSR3 were set to 38429302 Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals Sources: Literature |
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| Fetal anomalies v1.197 | THSD1 |
Zornitza Stark gene: THSD1 was added gene: THSD1 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: THSD1 were set to 33569873; 27895300 Phenotypes for gene: THSD1 were set to Lymphatic malformation 13, MIM# 620244 Review for gene: THSD1 was set to GREEN Added comment: PMID: 33569873 - 1 fetus with a homozygous PTC and nonimmune hydrops fetalis (NIHF), congenital heart disease and hemangiomas. FHx of 1/3 triplets with severe hydrops fetalis, not sequenced. - Paper reviews previous NIHF cases and reports another homozygous PTC in two families ( and a recurring homozygous missense (p.Cys206Tyr) in three families. PMID: 27895300- Mouse model has hydrocephaly with poor perfusion. Sources: Expert Review |
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| Fetal anomalies v1.191 | THOC2 | Zornitza Stark Phenotypes for gene: THOC2 were changed from Mental retardation, X-linked 12/35 MIM#300957 to Mental retardation, X-linked 12/35 MIM#300957; Arthrogryposis (MONDO:0008779), THOC2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.189 | THOC2 |
Zornitza Stark edited their review of gene: THOC2: Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal. Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle; Changed publications: 29851191, 34976470, 37945483; Changed phenotypes: Mental retardation, X-linked 12/35 MIM#300957, Arthrogryposis (MONDO:0008779), THOC2-related |
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| Fetal anomalies v1.186 | DLG5 |
Zornitza Stark gene: DLG5 was added gene: DLG5 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DLG5 were set to 32631816 Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703 Review for gene: DLG5 was set to GREEN Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations. Sources: Expert Review |
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| Fetal anomalies v1.179 | MAX |
Rylee Peters gene: MAX was added gene: MAX was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAX were set to 38141607 Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related Review for gene: MAX was set to GREEN Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain. Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae. Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc. Sources: Literature |
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| Fetal anomalies v1.174 | RAP1B | Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.173 | RAP1B | Zornitza Stark reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.170 | MMP13 | Zornitza Stark reviewed gene: MMP13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.167 | PKP2 |
Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome. Sources: Literature; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome. Sources: Literature |
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| Fetal anomalies v1.167 | PKP2 |
Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome. Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome. Sources: Literature |
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| Fetal anomalies v1.167 | PKP2 |
Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome. Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome. Sources: Literature |
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| Fetal anomalies v1.167 | PKP2 |
Suliman Khan gene: PKP2 was added gene: PKP2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PKP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PKP2 were set to PMID: 30562116; PMID: 35059364; PMID: 38050058 Phenotypes for gene: PKP2 were set to dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction Penetrance for gene: PKP2 were set to unknown Review for gene: PKP2 was set to GREEN Added comment: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed. PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD). PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome. Sources: Literature |
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| Fetal anomalies v1.166 | PLS3 | Zornitza Stark Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Bone mineral density QTL18, osteoporosis - MIM#300910; Diaphragmatic hernia 5, X-linked, MIM# 306950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.165 | PLS3 | Zornitza Stark reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 5, X-linked, MIM# 306950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.159 | ADAMTS15 | Zornitza Stark Phenotypes for gene: ADAMTS15 were changed from Arthrogryposis (MONDO:0008779), ADMATS15-related to Arthrogryposis, distal, type 12, MIM# 620545 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.158 | ADAMTS15 | Zornitza Stark edited their review of gene: ADAMTS15: Changed phenotypes: Arthrogryposis, distal, type 12, MIM# 620545 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.155 | PLS3 | Ain Roesley Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910 to Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.152 | PLS3 | Lauren Rogers reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37751738; Phenotypes: congenital diaphragmatic hernia MONDO:0005711, PLS3-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.151 | MYCN | Elena Savva Added comment: Comment on phenotypes: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals). Clinical presentation includes megalencephaly, hypoplastic corpus callosum, postaxial polydactyly, intellectual disability and motor delay. Knock-in mouse model showed morphological manifestations in multiple tissues including digits, female reproductive system and kidney. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.139 | CUL3 |
Lucy Spencer gene: CUL3 was added gene: CUL3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CUL3 were set to 37665043 Phenotypes for gene: CUL3 were set to Neurodevelopmental disorder with or without autism or seizures (MIM#619239); Pseudohypoaldosteronism, type IIE (MIM#614496) Review for gene: CUL3 was set to GREEN Added comment: PMID: 37665043 1 case study and a review of the literature. 5 patients with de novo variants (PTCs and missense) in CUL3 who have various cardiac phenotypes: atrial septal defects, left ventricular outflow tract obstruction. Hypertrophic right ventricle pulmonary atresia, and other congenital heart defects. 2 of these patients have a neurological phenotype as well, while the other three are not reported to have one (but at least one was a terminated pregnancy). Sources: Literature |
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| Fetal anomalies v1.132 | PHF5A |
Daniel Flanagan gene: PHF5A was added gene: PHF5A was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PHF5A were set to PMID: 37422718 Review for gene: PHF5A was set to GREEN Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects and heart defects, inguinal hernia, and sacral dimple in three subjects. Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects. Sources: Expert list |
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| Fetal anomalies v1.131 | SENP7 |
Elena Savva gene: SENP7 was added gene: SENP7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SENP7 were set to PMID: 37460201 Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related Review for gene: SENP7 was set to AMBER Added comment: PMID: 37460201 - 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically. - Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome. - Additional studies performed supporting downstream proteins expression being affected - Neutropenia observed in 2/3 patients Sources: Literature |
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| Fetal anomalies v1.120 | ERI1 |
Zornitza Stark gene: ERI1 was added gene: ERI1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ERI1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: ERI1 were set to 37352860 Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510) Review for gene: ERI1 was set to GREEN Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families - Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly - Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly - Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive - Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells - K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy with ERI1, staying bound to those RNA molecules" Sources: Literature |
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| Fetal anomalies v1.114 | DRG1 |
Dean Phelan gene: DRG1 was added gene: DRG1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DRG1 were set to PMID: 37179472 Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related Review for gene: DRG1 was set to GREEN Added comment: PMID: 37179472 - Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function. Sources: Literature |
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| Fetal anomalies v1.114 | RAB34 |
Sarah Pantaleo gene: RAB34 was added gene: RAB34 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAB34 were set to PMID: 37384395 Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies Penetrance for gene: RAB34 were set to Complete Review for gene: RAB34 was set to GREEN Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS. Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher). Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands. In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth. All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities. All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance. Sources: Literature |
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| Fetal anomalies v1.101 | KIF21A |
Chirag Patel gene: KIF21A was added gene: KIF21A was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF21A were set to PMID: 34740919 Phenotypes for gene: KIF21A were set to Severe fetal akinesia with arthrogryposis multiplex Review for gene: KIF21A was set to AMBER Added comment: 2 unrelated consanguineous Turkish families with 5 affected fetuses with severe fetal akinesia with arthrogryposis multiplex. WES identified different homozygous LOF variants in KIF21A gene (p.Leu449* and p.Arg791Glufs*8). Parents and a healthy sibling were heterozygous carriers. No functional studies. Sources: Literature |
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| Fetal anomalies v1.98 | FILIP1 | Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168 to Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.93 | ACTC1 | Lilian Downie reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36945405; Phenotypes: Atrial septal defect 5 MIM#612794, Cardiomyopathy, dilated, 1R MIM#613424, Cardiomyopathy, hypertrophic, 11 MIM#612098, ACTC1 related distal arthrogryposis MONDO:0019942; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.93 | ESAM |
Chern Lim gene: ESAM was added gene: ESAM was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESAM were set to 36996813 Phenotypes for gene: ESAM were set to Neurodevelopmental disorder (MONDO#0700092), ESAM-related Review for gene: ESAM was set to GREEN gene: ESAM was marked as current diagnostic Added comment: PMID 36996813 - Thirteen affected individuals, including four fetuses, from eight unrelated families, with homozygous loss-of-function-type variants in ESAM – 2 of the variants are frameshifts, 1x nonsense, 1x canonical splice. - Affected individuals have profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses. - One of the frameshift variant c.115del (p.Arg39Glyfs*33), was detected in six individuals from four unrelated families from the same geographic region in Turkey (southeastern Anatolia), suggesting a founder effect. - The c.451+1G>A variant was detected in three individuals from two independent families with the same ethnic origin (Arab Bedouin) Sources: Literature |
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| Fetal anomalies v1.93 | FILIP1 | Paul De Fazio edited their review of gene: FILIP1: Changed phenotypes: Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.93 | FILIP1 |
Paul De Fazio gene: FILIP1 was added gene: FILIP1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FILIP1 were set to 36943452 Phenotypes for gene: FILIP1 were set to Arthrogryposis multiplex congenita MONDO:0015168 Penetrance for gene: FILIP1 were set to unknown Review for gene: FILIP1 was set to GREEN gene: FILIP1 was marked as current diagnostic Added comment: 3 families, all consanguineous, reported with 3 different homozygous loss of function variants (2x NMD-predicted nonsense, 1x intragenic deletion of exons 3-6 of 6). In one family, the variant segregated in 3 affected siblings. Phenotypes consist of congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly (-1.5 to -4 SD), and facial dysmorphism. Sources: Literature |
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| Fetal anomalies v1.82 | SLC31A1 |
Daniel Flanagan gene: SLC31A1 was added gene: SLC31A1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171 Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092) Review for gene: SLC31A1 was set to AMBER Added comment: PMID:36562171 Homozygous c.236T>C; p.(Leu79Pro) identified in a newborn of consanguineous parents. Variant absent from gnomAD. Prenatal ultrasound showed a male fetus with short femoral bones, an apparently enlarged heart-to-thorax ratio, and a wide cisterna magna. The infant was born with pulmonary hypoplasia. At 2 weeks of age, multifocal brain hemorrhages were diagnosed and the infant developed seizures. The infant died at 1 month of age. The Mother had three healthy children while nine pregnancies had been extrauterine gravidities or ended in first or mid-trimester spontaneous abortions. PMID: 35913762 SLC31A1 is also referred to as CTR1. Monozygotic twins with hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. Homozygous for a novel missense variant (p.(Arg95His)) in copper transporter CTR1, both parents heterozygous. A mouse knock-out model of CTR1 deficiency resulted in prenatal lethality. Sources: Expert list |
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| Fetal anomalies v1.77 | SHROOM4 | Alison Yeung Classified gene: SHROOM4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.77 | SHROOM4 | Alison Yeung Gene: shroom4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.76 | SHROOM4 | Alison Yeung reviewed gene: SHROOM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 36379543; Phenotypes: Congenital anomaly of the kidney and urinary tracy (CAKUT), SHROOM4-related, MONDO:0019719; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.71 | KCNK3 |
Krithika Murali gene: KCNK3 was added gene: KCNK3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNK3 were set to 36195757 Phenotypes for gene: KCNK3 were set to Neurodevelopmental disorder, MONDO:0700092, KCNK3-related; developmental delay with sleep apnoea (DDSA) Review for gene: KCNK3 was set to GREEN Added comment: PMID 36195757 Sörmann et al 2022 report 9 unrelated individuals with de novo heterozygous KCNK3 missense variants (21 weeks to 25 years old). All 8 living probands (3-25 years) had hypotonia, global developmental delay, central and/or obstructive sleep apnoea and feeding difficulties. 7/9 probands had additional anomalies including microcephaly (at least 3/9), arthrogryposis/flexion contractures/foot deformities (7/9), scoliosis, cleft palate (2/9), and ambiguous genitalia/undescended testes (5/6) and dysmorphism. IUGR reported in 3/9 probands and polyhdramnios in 2/9. KCNK3 encodes the TASK-1 K2P channel expressed throughout the central nervous system. All identified variants clustered near the X-gate and are involved in inter- or intra-subunit interaction likely to hold the X-gate closed. Individuals with variants located in the M2 transmembrane helix had a more severe phenotype than those with variants in the M4 helix. Functional studies support a gain of function disease mechanism with increased channel activation. TASK-1 K+ channel inhibitors (some in clinical use) have been raised as a possible therapeutic strategy. ---- Heterozygous LoF variants associated with a different disorder - primary pulmonary arterial hypertension Sources: Literature |
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| Fetal anomalies v1.67 | ALDH1A2 | Zornitza Stark Phenotypes for gene: ALDH1A2 were changed from Multiple congenital anomalies, ALDH1A2-related, MONDO:0019042 to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.66 | ALDH1A2 | Zornitza Stark reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.64 | ADAMTS15 |
Zornitza Stark gene: ADAMTS15 was added gene: ADAMTS15 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS15 were set to 35962790 Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related Review for gene: ADAMTS15 was set to GREEN Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature |
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| Fetal anomalies v1.60 | NPNT |
Chirag Patel gene: NPNT was added gene: NPNT was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792 Phenotypes for gene: NPNT were set to Renal agenesis, no OMIM # Review for gene: NPNT was set to GREEN Added comment: 3 consanguineous families with multiple affecteds with bilateral renal agenesis. Whole-exome sequencing (WES)-based homozygosity mapping identified 2 homozygous truncating variants. Reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Loss of nephronectin (NPNT) is known to lead to failure of metanephric kidney development with resulting renal agenesis in murine models. Sources: Literature |
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| Fetal anomalies v1.54 | ZMYND8 |
Zornitza Stark gene: ZMYND8 was added gene: ZMYND8 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZMYND8 were set to 35916866; 32530565 Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures Review for gene: ZMYND8 was set to GREEN Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565). Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11). As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression. The protein is broadly expressed in brain and shows highest expression in early development. Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain). Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning. Sources: Expert Review |
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| Fetal anomalies v1.47 | GINS3 |
Zornitza Stark gene: GINS3 was added gene: GINS3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GINS3 were set to 35603789 Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related Review for gene: GINS3 was set to GREEN Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model. Sources: Literature |
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| Fetal anomalies v1.41 | WNT7B |
Zornitza Stark gene: WNT7B was added gene: WNT7B was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WNT7B were set to 35790350 Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related Review for gene: WNT7B was set to GREEN Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model. Sources: Literature |
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| Fetal anomalies v1.36 | ADD1 |
Zornitza Stark gene: ADD1 was added gene: ADD1 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: ADD1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: ADD1 were set to 34906466 Phenotypes for gene: ADD1 were set to Neurodevelopmental disorder MONDO:0700092, ADD1-related Review for gene: ADD1 was set to GREEN Added comment: 4 unrelated individuals affected by ID and/or complete or partial agenesis of corpus callosum, and enlarged lateral ventricles. WES found loss-of-function variants - 1 recessive missense variant and 3 de novo variants. The recessive variant is associated with ACC and enlarged lateral ventricles, and the de novo variants were associated with complete or partial agenesis of corpus callosum, mild ID and attention deficit. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes. Three adducin genes (ADD1, ADD2, and ADD3) encode cytoskeleton proteins that are critical for osmotic rigidity and cell shape. ADD1, ADD2, and ADD3 form heterodimers (ADD1/ADD2, ADD1/ADD3), which further form heterotetramers. Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown Sources: Expert Review |
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| Fetal anomalies v1.31 | USP14 | Zornitza Stark Phenotypes for gene: USP14 were changed from Distal arthrogryposis, corpus callosum anomalies, and dysmorphic features; no OMIM # to Syndromic disease MONDO:0002254, USP14-related; Distal arthrogryposis, corpus callosum anomalies, and dysmorphic features | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.29 | USP14 |
Chirag Patel gene: USP14 was added gene: USP14 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP14 were set to PMID: 35066879 Phenotypes for gene: USP14 were set to Distal arthrogryposis, corpus callosum anomalies, and dysmorphic features; no OMIM # Review for gene: USP14 was set to RED Added comment: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay. Sources: Literature |
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| Fetal anomalies v1.14 | TNNI1 | Zornitza Stark Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.13 | TNNI1 |
Krithika Murali gene: TNNI1 was added gene: TNNI1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TNNI1 were set to 34934811 Phenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures Review for gene: TNNI1 was set to AMBER Added comment: No OMIM gene disease association reported PMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant. The proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming. Trio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK. The affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts. Sources: Literature |
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| Fetal anomalies v0.4717 | CAPN15 |
Zornitza Stark gene: CAPN15 was added gene: CAPN15 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: CAPN15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAPN15 were set to 32885237 Phenotypes for gene: CAPN15 were set to Oculogastrointestinal neurodevelopmental syndrome, MIM# 619318; microphthalmia HP:0000568; coloboma HP:0000589 Review for gene: CAPN15 was set to GREEN Added comment: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families). Capn15 knockout mice showed similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth. Sources: Expert Review |
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| Fetal anomalies v0.4699 | NCAPD2 |
Zornitza Stark gene: NCAPD2 was added gene: NCAPD2 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NCAPD2 were set to 31056748; 27737959; 28097321 Phenotypes for gene: NCAPD2 were set to Microcephaly 21, primary, autosomal recessive; OMIM #617983 Review for gene: NCAPD2 was set to GREEN Added comment: Three families reported: 1 family with 2 sibs with microcephaly and ID, and homozygous NCAPD2 mutation, which segregated with disease. No functional evidence. 1 family with 1 affected and homozygous NCAPD2 mutation, which segregated with disease. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls. 1 family with 2 sibs with microcephaly, growth retardation, and ID, and homozygous NCAPD2 mutation, which segregated with disease. Functional studies of the variants and studies of patient cells were not performed. IUGR reported. Sources: Expert Review |
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| Fetal anomalies v0.4692 | NUP85 |
Zornitza Stark gene: NUP85 was added gene: NUP85 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP85 were set to 34170319 Phenotypes for gene: NUP85 were set to Microcephaly, MONDO:0001149, NUP85-related Review for gene: NUP85 was set to AMBER Added comment: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction. In the second family, compound heterozygous missense variants in NUP85 were detected (c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle. Variants in this gene are also associated with nephrotic syndrome. Sources: Expert Review |
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| Fetal anomalies v0.4686 | PRIM1 |
Belinda Chong gene: PRIM1 was added gene: PRIM1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRIM1 were set to 33060134 Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950 Review for gene: PRIM1 was set to AMBER gene: PRIM1 was marked as current diagnostic Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature |
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| Fetal anomalies v0.4686 | PPP1R15B |
Belinda Chong gene: PPP1R15B was added gene: PPP1R15B was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PPP1R15B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP1R15B were set to 26159176; 26307080; 27640355 Phenotypes for gene: PPP1R15B were set to Microcephaly, short stature, and impaired glucose metabolism 2, MIM# 616817 Review for gene: PPP1R15B was set to AMBER gene: PPP1R15B was marked as current diagnostic Added comment: Three unrelated families reported, two with the same variant. Phenotype in family reported in PMID 27640355 included infantile cirrhosis requiring transplantation. Sources: Literature |
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| Fetal anomalies v0.4682 | ANKS6 | Alison Yeung reviewed gene: ANKS6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 16, MIM# 615382, MONDO:0014158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4681 | ALDH1A2 | Alison Yeung Phenotypes for gene: ALDH1A2 were changed from Congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; thymus aplasia to Multiple congenital anomalies, ALDH1A2-related, MONDO:0019042 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4662 | NPHP1 | Zornitza Stark Phenotypes for gene: NPHP1 were changed from NEPHRONOPHTHISIS TYPE 1; JOUBERT SYNDROME TYPE 4; SENIOR-LOKEN SYNDROME TYPE 1 to Joubert syndrome 4, MIM# 609583 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4658 | NPHP3 | Zornitza Stark Phenotypes for gene: NPHP3 were changed from RENAL-HEPATIC-PANCREATIC DYSPLASIA; NEPHRONOPHTHISIS TYPE 3; MECKEL SYNDROME TYPE 7 to Meckel syndrome 7, MIM# 267010; Nephronophthisis 3, MIM# 604387; Renal-hepatic-pancreatic dysplasia 1, MIM# 208540 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4656 | NPHP3 | Zornitza Stark edited their review of gene: NPHP3: Changed phenotypes: Meckel syndrome 7, MIM# 267010, Nephronophthisis 3, MIM# 604387, Renal-hepatic-pancreatic dysplasia 1, MIM# 208540 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4654 | NPHP4 | Zornitza Stark Phenotypes for gene: NPHP4 were changed from NEPHRONOPHTHISIS TYPE 4 to Nephronophthisis 4, MIM# 606966; Senior-Loken syndrome 4, MIM# 606996 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4645 | NSDHL | Zornitza Stark Phenotypes for gene: NSDHL were changed from CK SYNDROME; CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS to CK syndrome , MIM#300831 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4642 | NUP107 | Zornitza Stark Phenotypes for gene: NUP107 were changed from EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME to Galloway-Mowat syndrome 7, MIM# 618348 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4626 | PEX11B | Zornitza Stark changed review comment from: Congenital cataracts.; to: Congenital cataracts. Three families altogether, two published, and one internal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4588 | PIEZO2 | Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Ataxia, dysmetria, contractures & scoliosis with normal cognition but loss of discriminative touch perception; ARTHROGRYPOSIS, DISTAL, TYPE 3 to Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4546 | PIGH |
Belinda Chong gene: PIGH was added gene: PIGH was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PIGH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGH were set to 29573052; 33156547; 29603516 Phenotypes for gene: PIGH were set to Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010 Review for gene: PIGH was set to AMBER gene: PIGH was marked as current diagnostic Added comment: Microcephaly appears to present at postnatal in these individuals. Three further families reported, including two sibs with microcephaly. Sources: Literature |
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| Fetal anomalies v0.4532 | PSAP | Zornitza Stark Phenotypes for gene: PSAP were changed from Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722, MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590; Gaucher disease, atypical, MIM# 610539, MONDO:0012517 to Combined SAP deficiency, MIM# 611721 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4513 | PRKD1 |
Zornitza Stark edited their review of gene: PRKD1: Added comment: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.' PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation. c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; Changed publications: 27479907, 32817298; Changed phenotypes: Congenital heart defects and ectodermal dysplasia, MIM#617364; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Fetal anomalies v0.4490 | RARB | Zornitza Stark Phenotypes for gene: RARB were changed from MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA to Microphthalmia, syndromic 12, MIM# 615524 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4486 | RARS2 | Zornitza Stark changed review comment from: Progressive microcephaly is part of the phenotype. At least three unrelated families reported.; to: Progressive microcephaly, PCH. At least three unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4481 | RBM8A | Zornitza Stark Phenotypes for gene: RBM8A were changed from THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME to Thrombocytopaenia-absent radius syndrome, MIM# 274000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4478 | MCM7 |
Krithika Murali gene: MCM7 was added gene: MCM7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM7 were set to 33654309; 34059554 Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency Review for gene: MCM7 was set to AMBER Added comment: Association with congenital microcephaly. No new publications since last PanelApp review --- MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present. ------ Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families. - PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment. Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression. - PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7. Sources: Literature |
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| Fetal anomalies v0.4478 | PSAP | Seb Lunke Phenotypes for gene: PSAP were changed from ATYPICAL KRABBE DISEASE to Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722, MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590; Gaucher disease, atypical, MIM# 610539, MONDO:0012517 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4476 | PSAP | Seb Lunke reviewed gene: PSAP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined SAP deficiency, MIM# 611721, Encephalopathy due to prosaposin deficiency, MONDO:0012719, Krabbe disease, atypical, MIM# 611722, MONDO:0012720, Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590, Gaucher disease, atypical, MIM# 610539, MONDO:0012517 Edit; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4409 | SDCCAG8 | Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from SENIOR-LOKEN SYNDROME 7 to Bardet-Biedl syndrome 16, MIM# 615993; MONDO:0014444; Senior-Loken syndrome 7, MIM# 613615; MONDO:0013326; Nephronophthisis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4407 | SEC23B | Zornitza Stark Phenotypes for gene: SEC23B were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II to Dyserythropoietic anemia, congenital, type II 224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4404 | RHEB |
Krithika Murali gene: RHEB was added gene: RHEB was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: RHEB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RHEB were set to 29051493; 31337748 Phenotypes for gene: RHEB were set to Intellectual disability; Macrocephaly; Focal cortical dysplasia Review for gene: RHEB was set to GREEN Added comment: No new publications since last PanelApp review. Reviewed PMID: 29051493 supplementary information - three individuals with short stature and macrocephaly. Limited antenatal information provided/birth HC parameters, but one of the affected individuals was noted to have a large head circumference from 20 weeks gestation. PMID 31337748: Somatic variant in this gene found in one individual with focal cortical dysplasia. --- 3 individuals from two families with heterozygous RHEB variants. Two siblings carried the c.110 C > T (p.Pro37Leu) variant, and a sporadic individual carried the c.202 T>C (p.Ser68Pro) allele. All 3 individuals had short stature (−2 to −3 SD) and early brain overgrowth with pronounced macrocephaly during childhood (+2.5/+3 SD). They had severe to profound ID with hypotonia, as well as autism spectrum disorder. 2 of 3 individuals were reported to have epilepsy. In a zebrafish model, overexpression of RHEB produced megalencephaly, supporting a hyperactivating effect. This is supported in mice where loss of RHEB activity does not cause an overt neurological phenotype Single individual with somatic variants in this gene and focal cortical dysplasia also reported. Sources: Literature |
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| Fetal anomalies v0.4392 | PPP2R5C |
Krithika Murali gene: PPP2R5C was added gene: PPP2R5C was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PPP2R5C were set to 25972378 Phenotypes for gene: PPP2R5C were set to macrocephaly; overgrowth Review for gene: PPP2R5C was set to AMBER Added comment: x1 case only in the literature with relative macrocephaly noted at birth. PMID: 25972378 - Loveday et al 2015 undertook trio exome sequencing in children with an overgrowth syndrome phenotype with unaffected parents. One individual with a de novo PPP2R5C c.468_470delAAC p.Thr157del variant identified. The proband had moderate ID, was born at 37 weeks gestation weighing 3100g (0.8SD) with a head circumference of 36cm (2.4SD). Sources: Literature |
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| Fetal anomalies v0.4311 | VPS4A |
Chirag Patel gene: VPS4A was added gene: VPS4A was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VPS4A were set to PMID: 33186543; 33186545 Phenotypes for gene: VPS4A were set to CIMDAG syndrome MIM# 619273 Review for gene: VPS4A was set to GREEN Added comment: CIMDAG syndrome is a multisystemic disorder characterized by severely impaired psychomotor development and hematologic abnormalities apparent from early infancy. Affected individuals show poor overall growth with microcephaly, impaired intellectual development, poor or absent speech, poor eye contact, and motor problems, such as inability to walk, hypotonia, and spasticity. Brain imaging typically shows cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination. The associated hematologic abnormalities are variable, but are mostly consistent with congenital dyserythropoietic anemia. Eight unrelated patients with de novo heterozygous missense mutations in the VPS4A gene. Sources: Expert list |
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| Fetal anomalies v0.4305 | VPS50 |
Chirag Patel gene: VPS50 was added gene: VPS50 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS50 were set to PMID: 34037727 Phenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685 Review for gene: VPS50 was set to AMBER Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. Sources: Expert list |
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| Fetal anomalies v0.4295 | YIF1B |
Chirag Patel gene: YIF1B was added gene: YIF1B was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to PMID: 32006098; 26077767 Phenotypes for gene: YIF1B were set to Kaya-Barakat-Masson syndrome, MIM# 619125 Review for gene: YIF1B was set to GREEN Added comment: Kaya-Barakat-Masson syndrome (KABAMAS) is a severe autosomal recessive neurodevelopmental disorder characterized by profoundly impaired global development, peripheral spasticity, dystonia, impaired intellectual development with absent speech, poor eye contact, and feeding difficulties, resulting in poor overall growth, sometimes with microcephaly. Additional more variable features include early-onset seizures, ocular anomalies, foot deformities, and nonspecific brain imaging findings, such as thin corpus callosum and cerebral, cerebellar, or pontine atrophy. Some patients may die in infancy or early childhood. 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. Sources: Expert list |
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| Fetal anomalies v0.4273 | INTS8 |
Daniel Flanagan gene: INTS8 was added gene: INTS8 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INTS8 were set to 28542170 Phenotypes for gene: INTS8 were set to Neurodevelopmental disorder with cerebellar hypoplasia and spasticity (MIM#618572) Review for gene: INTS8 was set to RED Added comment: Single family with three affected sibs with compound het INTS8 variants, Microcephaly, Cerebellar hypoplasia, Nodular heterotopia. Some functional evidence. Sources: Expert list |
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| Fetal anomalies v0.4273 | ERMARD |
Daniel Flanagan gene: ERMARD was added gene: ERMARD was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: ERMARD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ERMARD were set to 27087860; 24056535 Phenotypes for gene: ERMARD were set to Periventricular nodular heterotopia 6 (MIM#615544) Review for gene: ERMARD was set to RED Added comment: Single individual described with heterozygous ERMARD missense and periventricular nodular heterotopia, developmental delay and epilepsy. PMID: 27087860. Fetus was diagnosed by prenatal ultrasound with symmetric bilateral ventriculomegaly. The fetus carried a 0.78-Mb deletion of chromosomal region 6q27 (ERMARD included). Sources: Expert list |
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| Fetal anomalies v0.4273 | EOMES |
Daniel Flanagan gene: EOMES was added gene: EOMES was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: EOMES was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EOMES were set to 17353897 Phenotypes for gene: EOMES were set to microcephaly; polymicrogyria; corpus callosum agenesis Review for gene: EOMES was set to RED Added comment: Single family with homozygous balanced translocation between chromosomes 3p and 10q affecting EOMES. Sources: Expert list |
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| Fetal anomalies v0.4273 | FIBP |
Krithika Murali gene: FIBP was added gene: FIBP was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FIBP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FIBP were set to 27183861; 26660953 Phenotypes for gene: FIBP were set to Thauvin-Robinet-Faivre syndrome - MIM#617107 Review for gene: FIBP was set to AMBER Added comment: Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor. 2 unrelated families reported. 27183861 - report one family with 3 affected children. Prenatally relevant phenotypic features include: - congenital heart disease in one child - preterm delivery and bilateral talipes equinovarus 2nd child - cystic kidney disease, nephromegaly and polyhydramnios 3rd child 26660953 - report one child with ventricular septal defect, mitral valve prolapse, renal malrotation with left bifid ureter, macrocephaly and macrosomia noted at birth. Sources: Literature |
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| Fetal anomalies v0.4266 | ARF1 |
Daniel Flanagan gene: ARF1 was added gene: ARF1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARF1 were set to 28868155; 34353862 Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8 (MIM#618185) Review for gene: ARF1 was set to RED Added comment: Three unrelated individuals reported with de novo missense in this gene. PMID: 34353862: Additional report of affected parent and child. 1 patient had microcephaly in teens but normal head circumference at first examination. Sources: Literature |
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| Fetal anomalies v0.4266 | ATXN2L |
Krithika Murali gene: ATXN2L was added gene: ATXN2L was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ATXN2L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATXN2L were set to 33283965; 33057194 Phenotypes for gene: ATXN2L were set to macrocephaly; intellectual disability Review for gene: ATXN2L was set to AMBER Added comment: Combined data from three large exome groups identified several de novo variants, including frameshift and missense, in ATXN2L in patients with developmental delay (Kaplanis et al., 2020). pLI=1.0 33283965 - Single case report of a novel de novo missense variant in a child with macrocephaly and developmental delay. No functional work. Macrocephaly was detected prenatally. This together with breech presentation resulted in elective C-section at 36 weeks. Sources: Literature |
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| Fetal anomalies v0.4264 | C7orf43 |
Ain Roesley gene: C7orf43 was added gene: C7orf43 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C7orf43 were set to 30715179 Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351 Penetrance for gene: C7orf43 were set to Complete Review for gene: C7orf43 was set to AMBER gene: C7orf43 was marked as current diagnostic Added comment: HGNC approved name TRAPPC14 Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model. Occipital-frontal circumferences were below2 SD at birth, with microcephaly progressing later in life Sources: Literature |
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| Fetal anomalies v0.4253 | SYT2 |
Belinda Chong gene: SYT2 was added gene: SYT2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SYT2 were set to 25192047; 32776697; 32250532; 30533528 Phenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461 Review for gene: SYT2 was set to GREEN gene: SYT2 was marked as current diagnostic Added comment: Myasthenic syndrome bi-allelic #619461- Decreased fetal movements Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. 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. Sources: Literature |
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| Fetal anomalies v0.4245 | NEB | Alison Yeung Phenotypes for gene: NEB were changed from AUTOSOMAL RECESSIVE TYPICAL NEMALINE MYOPATHY to Arthrogryposis multiplex congenita 6, MIM# 619334 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4237 | LAMA5 |
Belinda Chong gene: LAMA5 was added gene: LAMA5 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LAMA5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: LAMA5 were set to 33242826; 29534211; 16790509; 30589377; 28735299; 30631761 Phenotypes for gene: LAMA5 were set to bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay Review for gene: LAMA5 was set to RED Added comment: Currently amber gene and appears postnatal onset (not enough information) PMID: 29534211 - Three consanguineous families with homozygous missense variants (VUS) identified in two affected siblings with paediatric nephrotic syndrome within each family. No functional studies conducted on the missense variants. PMID: 16790509 - A hypomorphic Lama5 homozygous mouse model demonstrated proteinuria, cystic kidney disease and death from progressive renal failure at 3–4 weeks of age. PMID: 24130771 - a single case focal segmental glomerulosclerosis (proteinuria) with biallelic missense variants (VUS - S1469A & V2440I). Also reports p.Gly3685Arg in 2 other cases, which has 11 homozygotes in gnomAD v2.1 PMID: 29764427, 30808327 - Four families with haematuria and proteinuria reported with digenic inheritance of a LAMA5 missense variant with a COL4A4/5 variant. One of those variants (p.His1717Tyr) has 892 homozygotes in gnomAD v2.1 PMID: 28735299, 30589377 - A single large multigenerational family with a multisystem syndrome (including ophthalmic fetures), segregating a heterozygous missense p.V3140M, and supporting knock-in mouse model that recapitulates the phenotype. PMID: 33242826 - A single family with a bent bone dysplasia in 3 affected siblings with biallelic variants, and some supporting in vitro functional assays. PMID: 28544784, 29377152 - Single family with congenital myasthenic syndrome with a homozygous missense reported twice. PMID: 30631761 - a single case with a de novo splice site variant with developmental delay, epilepsy, and hypotonia Sources: Literature |
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| Fetal anomalies v0.4229 | MYRF | Alison Yeung Phenotypes for gene: MYRF were changed from Congenital diaphragmatic hernia (CDH); Cardiac-urogenital syndrome, 618280; Disorders of sex development (DSD) to Cardiac-urogenital syndrome, MIM# 618280 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4224 | SON | Zornitza Stark Phenotypes for gene: SON were changed from Intellectual Disability, Congenital Malformations, and Failure to Thrive to ZTTK syndrome, MIM# 617140 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4200 | ATN1 |
Krithika Murali gene: ATN1 was added gene: ATN1 was added to Fetal anomalies. Sources: Literature,Expert list Mode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATN1 were set to 34212383; 30827498 Phenotypes for gene: ATN1 were set to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies - MIM#618494 Review for gene: ATN1 was set to GREEN Added comment: Monoallelic variants associated with syndromic ID. Phenotypic features include arthrogryposis, epilepsy and congenital malformations of the brain, heart, and genitourinary systems. Sources: Literature, Expert list |
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| Fetal anomalies v0.4189 | SCNN1B |
Chirag Patel gene: SCNN1B was added gene: SCNN1B was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SCNN1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SCNN1B were set to PubMed: 8589714 Phenotypes for gene: SCNN1B were set to Pseudohypoaldosteronism, type I - MIM#264350 Review for gene: SCNN1B was set to GREEN Added comment: Autosomal recessive pseudohypoaldosteronism type I caused by homozygous or compound heterozygous mutation in SCNN1B is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Multiple patients reported. Sources: Literature |
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| Fetal anomalies v0.4187 | SCNN1A |
Chirag Patel gene: SCNN1A was added gene: SCNN1A was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SCNN1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SCNN1A were set to PubMed: 8589714, 31301676 Phenotypes for gene: SCNN1A were set to Pseudohypoaldosteronism, type I - MIM#264350 Review for gene: SCNN1A was set to GREEN Added comment: Autosomal recessive pseudohypoaldosteronism type I caused by homozygous or compound heterozygous mutation in SCNN1A is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Multiple patients reported. Sources: Literature |
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| Fetal anomalies v0.4182 | NME8 |
Chirag Patel gene: NME8 was added gene: NME8 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NME8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NME8 were set to PubMed: 12032915, 12483741, 12928894 Phenotypes for gene: NME8 were set to CINCA syndrome, OMIM # 607115 Review for gene: NME8 was set to GREEN Added comment: Chronic infantile neurologic cutaneous and articular (CINCA) syndrome also known as 'neonatal onset multisystem inflammatory disease,' or NOMID, is a rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. 14 families with heterozygous missense mutations in exon 3. Presenting perinatally so suitable for fetal anomalies panel. Sources: Literature |
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| Fetal anomalies v0.4178 | MBTPS1 |
Chirag Patel gene: MBTPS1 was added gene: MBTPS1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBTPS1 were set to PMID: 32857899; 32420688; 30046013 Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia, no OMIM # Review for gene: MBTPS1 was set to GREEN Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature. Sources: Expert list |
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| Fetal anomalies v0.4176 | HOXA11 |
Chirag Patel gene: HOXA11 was added gene: HOXA11 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: HOXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HOXA11 were set to PubMed: 11101832 Phenotypes for gene: HOXA11 were set to Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 , OMIM #605432 Review for gene: HOXA11 was set to AMBER Added comment: Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm. A heterozygous mutation in the HOXA11 gene was found in affected members of 2 families segregating radioulnar synostosis and amegakaryocytic thrombocytopenia. Sources: Literature |
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| Fetal anomalies v0.4168 | PRDM15 |
Chirag Patel gene: PRDM15 was added gene: PRDM15 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRDM15 were set to PMID: 31950080 Phenotypes for gene: PRDM15 were set to Holoprosenephaly; Steroid resistant nephrotic syndrome; Multiple congenital anomalies Review for gene: PRDM15 was set to AMBER Added comment: Four consanguineous families reported with same homozygous variant, C844Y, shown to be LoF. Syndromic HPE including SRNS, brain malformations, polydactyly, congenital heart disease. Mouse model, extensive functional data. Two additional homozygous missense identified with isolated SRNS. Sources: Expert list |
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| Fetal anomalies v0.4163 | RAP1B |
Chirag Patel gene: RAP1B was added gene: RAP1B was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: RAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAP1B were set to PMID: 32627184; 26280580 Phenotypes for gene: RAP1B were set to Syndromic intellectual disability; short stature Review for gene: RAP1B was set to GREEN Added comment: Three unrelated individuals reported, Kabuki-like disorder (multiple malformations, microcephaly, learning difficulties, dysmorphism and other features). Sources: Literature |
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| Fetal anomalies v0.4161 | RAD50 |
Chirag Patel gene: RAD50 was added gene: RAD50 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: RAD50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAD50 were set to PMID: 19409520; 32212377; 33378670 Phenotypes for gene: RAD50 were set to Nijmegen breakage syndrome-like disorder, MIM# 613078; MONDO:0013118 Review for gene: RAD50 was set to GREEN Added comment: Nijmegen breakage syndrome-like disorder (NBSLD) is an autosomal recessive disorder characterized by severe prenatal growth retardation and persistent postnatal growth restriction, congenital microcephaly, borderline to mildly impaired intellectual development, normal sexual development, and radioresistant DNA synthesis with no immunodeficiency, myelodysplasia, or early neurodegeneration. Three unrelated families reported. Sources: Expert list |
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| Fetal anomalies v0.4155 | DNA2 |
Chirag Patel gene: DNA2 was added gene: DNA2 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNA2 were set to PMID: 24389050; 31045292 Phenotypes for gene: DNA2 were set to Seckel syndrome 8, MIM#615807 Review for gene: DNA2 was set to GREEN Added comment: Three families described with bi-allelic variants in this gene and a primordial dwarfism/Seckel syndrome phenotype (intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance). Note this gene is associated with multiple phenotypes. Sources: Expert list |
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| Fetal anomalies v0.4145 | CFAP45 |
Chirag Patel gene: CFAP45 was added gene: CFAP45 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: CFAP45 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP45 were set to PMID: 33139725 Phenotypes for gene: CFAP45 were set to Heterotaxy, visceral, 11, autosomal, with male infertility, MIM#619608 Review for gene: CFAP45 was set to GREEN Added comment: Three unrelated individuals reported with bi-alleic LOF variants, mouse model recapitulated phenotype. Sources: Expert list |
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| Fetal anomalies v0.4143 | EDN3 |
Chirag Patel gene: EDN3 was added gene: EDN3 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: EDN3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: EDN3 were set to PMID: 8630502; 11303518; 9359047; 10231870; 30171849; 27370713 Phenotypes for gene: EDN3 were set to Central hypoventilation syndrome, congenital, MIM# 209880; Waardenburg syndrome, type 4B, MIM# 613265; {Hirschsprung disease, susceptibility to, 4}, MIM# 613712 Review for gene: EDN3 was set to GREEN Added comment: Variants in this gene have been reported in both isolated HD and syndromic HD, variable penetrance. However, the variants reported in PMID 9359047 with isolated HD are present at high frequencies in gnomad: p.Ala17Thr >800 hets in gnomad, p.Ala224Thr >100 hets. Association with syndromic neural crest disorders is more definitive, and HD is reported in a proportion of individuals. Sources: Expert list |
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| Fetal anomalies v0.4132 | ALG14 |
Belinda Chong gene: ALG14 was added gene: ALG14 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ALG14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALG14 were set to 23404334; 28733338; 30221345; 23404334; 28733338 Phenotypes for gene: ALG14 were set 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 Review for gene: ALG14 was set to GREEN gene: ALG14 was marked as current diagnostic Added comment: Three OMIM disorders however, only Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036 with prenatal manifestations. 5 individuals from unrelated families described in the literature: one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype; and three more with a neurodegenerative phenotype. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation. The three OMIM disorders may represent a spectrum of severity for CDG. Sources: Literature |
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| Fetal anomalies v0.4126 | SPG11 |
Zornitza Stark changed review comment from: Bi-alllelic variants in this gene also cause spastic paraplegia-11 (OMIM# 604360) but also juvenile amyotrophic lateral sclerosis-5 (OMIM# 602099), and CMT2X. Same variants have been reported in association with different phenotypes, poor genotype-phenotype correlation. Recent review of >300 individuals with SPG11-related disease. Mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and intellectual disability (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%).; to: Bi-alllelic variants in this gene also cause spastic paraplegia-11 (OMIM# 604360) but also juvenile amyotrophic lateral sclerosis-5 (OMIM# 602099), and CMT2X. Same variants have been reported in association with different phenotypes, poor genotype-phenotype correlation. Recent review of >300 individuals with SPG11-related disease. Mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and intellectual disability (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%). Although onset of clinical features is typically in childhood or later, absent CC/CC abnormalities reported. |
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| Fetal anomalies v0.4119 | SRD5A3 | Zornitza Stark Phenotypes for gene: SRD5A3 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to Congenital disorder of glycosylation, type Iq, MIM# 612379; Kahrizi syndrome, MIM# 612713 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4100 | TBCD | Zornitza Stark changed review comment from: CC abnormalities.; to: CC abnormalities, arthrogryposis are relevant to fetal panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4083 | TCTN3 | Zornitza Stark Phenotypes for gene: TCTN3 were changed from MOHR-MAJEWSKI SYNDROME to Joubert syndrome 18, OMIM #614815; Orofaciodigital syndrome IV, OMIM #258860 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4053 | TMEM67 | Zornitza Stark Phenotypes for gene: TMEM67 were changed from COACH SYNDROM; JOUBERT SYNDROME TYPE 6; MECKEL SYNDROME TYPE 3; NEPHRONOPHTHISIS TYPE 11 to Joubert syndrome 6, MIM# 610688; Meckel syndrome 3, MIM# 607361 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4051 | TOP3A | Zornitza Stark Phenotypes for gene: TOP3A were changed from Bloom Syndrome like Disorder to Microcephaly, growth restriction, and increased sister chromatid exchange 2, MIM# 618097 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4047 | TPM2 | Zornitza Stark Phenotypes for gene: TPM2 were changed from Arthrogryposis multiplex congenita, distal, type 1, 108120; Arthrogryposis, distal, type 2B, 601680; ARTHROGRYPOSIS, DISTAL, TYPE 1 to Arthrogryposis multiplex congenita, distal, type 1, 108120; Arthrogryposis, distal, type 2B, 601680; Multiple pterygium syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4029 | TTC21B | Zornitza Stark Phenotypes for gene: TTC21B were changed from Short-rib thoracic dysplasia 4 with or without polydactyly 613819 to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4025 | TTN | Zornitza Stark Phenotypes for gene: TTN were changed from congenital titinopathy with arthrogryposis to Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4006 | VIPAS39 | Zornitza Stark Phenotypes for gene: VIPAS39 were changed from ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM #613404 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4004 | VIPAS39 | Zornitza Stark reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM #613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4002 | VPS33B | Zornitza Stark Phenotypes for gene: VPS33B were changed from ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1 to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3996 | WDR19 | Zornitza Stark Phenotypes for gene: WDR19 were changed from CRANIOECTODERMAL DYSPLASIA 4; ASPHYXIATING THORACIC DYSTROPHY 5 to Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307; Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376; Cranioectodermal dysplasia 4, MIM# 614378 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3994 | WDR19 | Zornitza Stark edited their review of gene: WDR19: Changed rating: GREEN; Changed publications: 33946315, 33875766, 33606107, 22019273, 23559409, 23683095, 32055034; Changed phenotypes: Nephronophthisis 13, MIM# 614377, Senior-Loken syndrome 8, MIM# 616307, Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376, Cranioectodermal dysplasia 4, MIM# 614378 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3955 | TIMM8A | Zornitza Stark Phenotypes for gene: TIMM8A were changed from JENSEN SYNDROME; MOHR-TRANEBJAERG SYNDROME to Mohr-Tranebjaerg syndrome, MIM# 304700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3954 | TIMM8A | Zornitza Stark reviewed gene: TIMM8A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mohr-Tranebjaerg syndrome, MIM# 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3951 | TGFB1 |
Zornitza Stark changed review comment from: Three individuals from two unrelated families reported. DD/ID and seizures in addition to IBD/immunodeficiency. Sources: Expert list; to: Three individuals from two unrelated families reported. DD/ID and seizures in addition to IBD/immunodeficiency, clinical presentation is typically post-natal. |
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| Fetal anomalies v0.3951 | TERT | Zornitza Stark Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal recessive 4 to Dyskeratosis congenita, autosomal recessive 4, OMIM #613989; Hoyeraal-Hreidarsson syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3940 | SLC9A6 | Zornitza Stark Phenotypes for gene: SLC9A6 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; MONDO:0010278 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3928 | SHROOM4 | Zornitza Stark Marked gene: SHROOM4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3928 | SHROOM4 | Zornitza Stark Gene: shroom4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3928 | SHROOM4 | Zornitza Stark edited their review of gene: SHROOM4: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3928 | SHROOM4 | Zornitza Stark Classified gene: SHROOM4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3928 | SHROOM4 | Zornitza Stark Gene: shroom4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3927 | SHROOM4 | Zornitza Stark edited their review of gene: SHROOM4: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3927 | SHROOM4 | Zornitza Stark changed review comment from: Two families only, clinical presentation is typically post-natal.; to: Two families only, clinical presentation is typically post-natal; there are only two P/LP variants in this gene in ClinVar. Fetus identified as part of an ACC cohort with LoF variant in SHROOM4, PMID 32565546. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3927 | SHROOM4 | Zornitza Stark edited their review of gene: SHROOM4: Changed publications: 16249884, 26740508, 32565546 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3927 | SHROOM4 | Zornitza Stark Publications for gene: SHROOM4 were set to 32565546 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3926 | SHROOM4 | Zornitza Stark edited their review of gene: SHROOM4: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3908 | RASA2 |
Krithika Murali gene: RASA2 was added gene: RASA2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: RASA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RASA2 were set to 25049390 Phenotypes for gene: RASA2 were set to Noonan syndrome Review for gene: RASA2 was set to AMBER Added comment: No OMIM gene disease association. Borderline red-amber gene. No new publications since last PanelApp review in 2020 -- One previous paper from 2014 described 3 patients with Noonan Syndrome and novel variants in RASA2. No segregation or functional data on the specific variants was provided. One of the three patients had an alternative variant in a different candidate gene. A more recent review using ClinGen criteria (2018) only found the disease association to have limited evidence, with no further patients identified since the 2014 paper, and none since. Sources: Literature |
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| Fetal anomalies v0.3908 | MAPK1 |
Krithika Murali gene: MAPK1 was added gene: MAPK1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAPK1 were set to 32721402 Phenotypes for gene: MAPK1 were set to Noonan syndrome 13 - MIM#619087 Review for gene: MAPK1 was set to GREEN Added comment: Associated with Noonan syndrome including congenital heart defects. No new publications since last PanelApp review Aug 2020 -- Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants. The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once. MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway. MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic). The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome). Sources: Literature |
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| Fetal anomalies v0.3908 | PLOD3 |
Krithika Murali gene: PLOD3 was added gene: PLOD3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PLOD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLOD3 were set to 30237576; 18834968 Phenotypes for gene: PLOD3 were set to Lysyl hydroxylase 3 deficiency - MIM#612394 Review for gene: PLOD3 was set to GREEN Added comment: 4 unrelated families reported with biallelic PLOD3 variants and Stickler-syndrome like phenotype including antenatal phenotype of IUGR in one family. -- PMID 30237576 Maddirevula et al 2019 - report homozygous nonsense variant in a proband with dysmorphic facies, microcephaly, ptosis and contractures. No antenatal information provided. PMID 31129566 Ewans et al 2019 - report 3 affected siblings with a Stickler-syndrome like disorder. - Patient 1 had congenital nystagmus and presented with hearing loss and myopia. On examination aged 2, noted to have dysmorphic features - prominent eyes, hypertelorism, malar hypoplasia, an upturned nose, low-set ears and microretrognathia. - Patient 2 noted to have camptodactyly and clinodactyly postnatally. On examination age 5 noted to have DIP joint contractures and mild skin syndactyly. - Patient 3 - breech delivery. bilateral hand foot camptodactyly, facial dysmorphism. - No antenatal features reported. PMID 30463024 Vahidnehzad et al 2019 - report a male proband from a consanguineous Iranian Baloch family referred for assessment age 4.5. Noted to have developmental delay, musculoskeletal manifestations including scoliosis, flexion contractions, cutaneous syndactyly, right diaphragmatic eventration, ocular anomalies, growth failure and skin blisters. No concerns antenatally. Postnatally noted to have cataract and facial dysmorphism (midface hypoplasia). Homozygous PLOD3 missense variant identified, parents unaffected carriers. PLOD3 mRNA levels in the patient’s fibroblasts measured by whole-transcriptome sequencing and confirmed by RT-PCR, were the same as in control cells, however, the expression of type VII collagen was reduced significantly. No antenatal features reported. PMID: 18834968 Salo et al 2008 - a female proband with significant IUGR, characteristic craniofacial profile, diaphragm eventration, skeletal anomalies (bilateral talipes equinovarus, flexion contractures, scoliosis from age 7), skin anomalies incl blistering and ocular anomalies. One 28 week male stillborn sibling noted to have significant IUGR and skeletal anomalies on post-mortem. Supportive functional evidence. Compound het PLOD3 variants. Sources: Literature |
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| Fetal anomalies v0.3908 | LOXL3 |
Krithika Murali gene: LOXL3 was added gene: LOXL3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LOXL3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LOXL3 were set to 25663169; 26307084; 26957899; 29802726; 30362103; 34787502 Phenotypes for gene: LOXL3 were set to Stickler syndrome; cleft lip/palate Review for gene: LOXL3 was set to AMBER Added comment: Biallelic variants reported in association with Stickler syndrome in 2 unrelated families. Also identified in one individual with non-syndromic Pierre Robin sequence who had a CNV also. --- PMID 34787502 Sood et al 2021 - proband with non-syndromic Pierre Robin sequence - homozygous missense LOXL3 variant identified. Sibling also had non-syndromic PRS, but genetic testing declined by family. In addition 551 kb chr10q26.2 duplication identified, no parental testing information provided, not previously reported to be associated with CL/P. PMID 30362103 Chan et al 2019 - report father and son with Stickler syndrome and homozygous LOXL3 missense variants. Predominantly ocular phenotype with no antenatal features reported. PMID: 29802726 Khan et al 2018 - genotyping of 258 probands with non-syndromic cleft palate (nsCP) and their parents, focusing in particular on common missense variant p.Ile615Phe. Identified four Phe/Phe homozygotes, report significant association between infant’s homozygote Phe/Phe genotype and the risk of nsCP, compared to common Ile/Ile homozygotes PMID 26957899 Li et al 2016 - A homozygous frameshift mutation (c.39dup; p.L14Afs*21) and a compound heterozygous frameshift mutation (c.39dup; p.L14Afs*21 and c.594delG; p.Q199Kfs*35) in LOXL3 were separately identified in two of 298 probands with early-onset high myopia. PMID: 26307084 Zhang et al 2015 - Mice lacking LOXL3 exhibited perinatal lethality and were noted to have cleft palate and spinal deformity. PMID: 25663169 Alzahrani et al 2015 - homozygous variant identified in 2 children with Stickler syndrome from the same family, both children had cleft lip/palate. Sources: Literature |
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| Fetal anomalies v0.3906 | SCN1A | Zornitza Stark changed review comment from: Arthrogryposis reported.; to: Arthrogryposis and malformations of cortical development reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3905 | SCN1A | Zornitza Stark edited their review of gene: SCN1A: Added comment: Arthrogryposis reported.; Changed publications: 33820833 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3831 | MPZ |
Zornitza Stark edited their review of gene: MPZ: Added comment: Variants in this gene are associated with various types of neuropathy, most with post-natal onset. However, at the severe end of the spectrum can present antenatally with decreased fetal movements and arthrogryposis.; Changed rating: GREEN; Changed phenotypes: Hypomyelinating neuropathy, congenital, 2, MIM# 618184; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Fetal anomalies v0.3826 | TSHR | Zornitza Stark Marked gene: TSHR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3826 | TSHR | Zornitza Stark Gene: tshr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3826 | TSHR | Zornitza Stark Classified gene: TSHR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3826 | TSHR | Zornitza Stark Gene: tshr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3825 | TSHR |
Krithika Murali gene: TSHR was added gene: TSHR was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TSHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TSHR were set to 23295291; 9360555; 7800007; 18655531; 15163335 Phenotypes for gene: TSHR were set to Hyperthyroidism, nonautoimmune - MIM#609152; Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200 Review for gene: TSHR was set to GREEN Added comment: Heterozygous variants associated with hyperthyroidism. De novo GoF variants in particular associated with more severe, non-autoimmune congenital hyperthyroidism. Biallelic LoF variants associated with congenital hypothyroidism. Premature delivery, IUGR and fetal tachycardia are reported antenatal phenotypes. Goitre also noted at birth in some cases. Craniosynostosis also a feature, but diagnosed postnatally in the context of rapidly advancing bone age. --- PMID: 9360555 Holzapfel 1997 - report IUGR and antenatal fetal tachycardia PMID: 7800007 Kopp et al 1995 - proband born prematurely at 32 weeks gestation with BW of 1660g. Fetal tachycardia and diffuse goitre noted postnatally. PMID: 18655531 Chester et al 2008 - proband born at 34 weeks. Antenatal ultrasound had shown thickened nuchal fold. PMID: 15163335 Vaidya et al 2004 - report two siblings born premature with IUGR, heterozygous variant inherited from affected father. Sources: Literature |
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| Fetal anomalies v0.3819 | MECP2 | Zornitza Stark Phenotypes for gene: MECP2 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 13; MENTAL RETARDATION SYNDROMIC X-LINKED LUBS TYPE; CHROMOSOME XQ28 DUPLICATION SYNDROME; ENCEPHALOPATHY NEONATAL SEVERE DUE TO MECP2 MUTATIONS; RETT SYNDROME (RTT)[ to Rett syndrome, MIM# 312750; Encephalopathy, neonatal severe 300673 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3800 | THRB | Zornitza Stark Marked gene: THRB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3800 | THRB | Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3800 | THRB | Zornitza Stark Classified gene: THRB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3800 | THRB | Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3799 | THRB | Zornitza Stark reviewed gene: THRB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3759 | RTEL1 | Zornitza Stark Phenotypes for gene: RTEL1 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 5; DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT 4 to Dyskeratosis congenita, autosomal recessive 5 MIM#615190; Hoyeraal-Hreidarsson syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3726 | PRG4 | Chirag Patel reviewed gene: PRG4: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 10545950, 29397575; Phenotypes: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome, OMIM #208250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3726 | THRB |
Krithika Murali gene: THRB was added gene: THRB was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: THRB was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: THRB were set to 35130567; 30430796; 30074255; 28938413; 4163616 Phenotypes for gene: THRB were set to Thyroid hormone resistance, autosomal recessive - MIM#274300; Thyroid hormone resistance - MIM#188570; Thyroid hormone resistance, selective pituitary - MIM#145650 Review for gene: THRB was set to GREEN Added comment: Biallelic variants associated with thyroid hormone resistance. PMID 4163616 first reported this condition in a consanguineous Mexican family with congenital deafness, goitre and stippled epiphyses. Diagnosis was made incidentally at a later age but possibility of goitre being detected antenatally. SGA also reported but this is generally in the context of having a mother also affected by thyroid hormone resistance secondary to biallelic or monoallelic variants. Sources: Literature |
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| Fetal anomalies v0.3721 | PROP1 |
Krithika Murali gene: PROP1 was added gene: PROP1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PROP1 were set to 15941866; 11549703; 20301521; 32415500 Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined, 2- #262600 Review for gene: PROP1 was set to AMBER Added comment: Biallelic variants associated with panhypopituitarism. Features include central congenital hypothyroidism and hypogonadotrophic hypogonadism including micropenis. Diagnosed postnatally in infancy or early childhood due to growth failure and failure to thrive. Antenatal diagnosis not reported, although severe micropenis due to other disorders has been detected antenatally. Sources: Literature |
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| Fetal anomalies v0.3670 | GHR | Zornitza Stark Marked gene: GHR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3670 | GHR | Zornitza Stark Gene: ghr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3670 | GHR | Zornitza Stark Phenotypes for gene: GHR were changed from PITUITARY DWARFISM II to Growth hormone insensitivity, partial, MIM#604271; Laron dwarfism, MIM#262500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3669 | GHR | Zornitza Stark Publications for gene: GHR were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3668 | GHR | Zornitza Stark Mode of inheritance for gene: GHR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3667 | GHR | Zornitza Stark Classified gene: GHR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3667 | GHR | Zornitza Stark Gene: ghr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3666 | GHR | Zornitza Stark edited their review of gene: GHR: Added comment: Birth weight and length are significantly decreased in the more severe, bi-allelic disorder (Laron).; Changed rating: GREEN; Changed publications: 9360502 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3613 | DEAF1 |
Zornitza Stark changed review comment from: Bi-allelic disease is through LOF mechanism (PTVs and missense). Mono-allelic disease described in association with de novo missense variants only. LOF and Dominant-negative - De novo missense in the SAND domain tend to have a dominant-negative effect - Biallelic variants in the SAND domain lead to partial loss of function - missense (reduced function), NMD (haploinsufficiency) - Heterozygous deletions have no phenotype.; to: Bi-allelic disease is through LOF mechanism (PTVs and missense). Mono-allelic disease described in association with de novo missense variants only. LOF and Dominant-negative - De novo missense in the SAND domain tend to have a dominant-negative effect - Biallelic variants in the SAND domain lead to partial loss of function - missense (reduced function), NMD (haploinsufficiency) - Heterozygous deletions have no phenotype. Brain abnormalities on imaging, particularly with AD disorder. |
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| Fetal anomalies v0.3588 | MYH3 | Zornitza Stark reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM #193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM #618436, Contractures, pterygia, and variable skeletal fusions syndrome 1A, OMIM #178110, Contractures, pterygia, and variable skeletal fusions syndrome 1B, OMIM #618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3587 | MYH3 | Alison Yeung Phenotypes for gene: MYH3 were changed from DISTAL ARTHROGRYPOSIS TYPE 2A; DISTAL ARTHROGRYPOSIS TYPE 2B to Arthrogryposis, distal, type 2A (Freeman-Sheldon) MIM# 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) MIM# 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, MIM#178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, MIM# 618469 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3580 | RPL10 |
Zornitza Stark changed review comment from: At least three families reported. Progressive microcephaly, up to -9.6 SD described. Sources: Expert list; to: At least three families reported. Progressive microcephaly, up to -9.6 SD described. IUGR, congenital heart disease. Sources: Expert list |
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| Fetal anomalies v0.3551 | RAD51 |
Zornitza Stark changed review comment from: Three unrelated individuals reported with de novo variants in this gene and FA phenotype. However, only one had radial ray abnormalities. Sources: Expert Review; to: Three unrelated individuals reported with de novo variants in this gene and FA phenotype. Sources: Expert Review |
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| Fetal anomalies v0.3541 | WNT9B |
Krithika Murali gene: WNT9B was added gene: WNT9B was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: WNT9B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WNT9B were set to 34145744 Phenotypes for gene: WNT9B were set to Renal agenesis/hypoplasia/dysplasia, no OMIM # Review for gene: WNT9B was set to AMBER Added comment: Now new publications since last PanelApp review Sept 2021 --- WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. WNT9B−/− mice have renal agenesis/hypoplasia and reproductive tract abnormalities. Lemire et al. (2021) report 4 individuals from 2 unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 had bilateral renal cystic dysplasia and chronic kidney disease, with 2 deceased siblings with bilateral renal hypoplasia/agenesis. The 3 affected family members were homozygous for a Gly317Arg missense variant in WNT9B. Proband from Family 2 had renal hypoplasia/dysplasia, chronic kidney disease, and was homozygous for a Pro5Alafs*52 nonsense variant in WNT9B. The proband's unaffected brother is also homozygous for the nonsense variant in WNT9B, suggesting nonpenetrance. Sources: Literature |
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| Fetal anomalies v0.3510 | TBC1D1 |
Krithika Murali gene: TBC1D1 was added gene: TBC1D1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TBC1D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TBC1D1 were set to 26572137 Phenotypes for gene: TBC1D1 were set to CAKUT Review for gene: TBC1D1 was set to GREEN Added comment: No new publications since last PanelApp review included below --- 1 heterozygous de novo frameshift variant in TBC1D1 in 1 CAKUT. 3 further CAKUT cases with three novel or rare inherited heterozygous TBC1D1 missense variants predicted to be pathogenic. TBC1D1 mutations affected Ser237-phosphorylation or protein stability and thereby act as hypomorphs. Tbc1d1 showed widespread expression in the developing murine urogenital system. A mild CAKUT spectrum phenotype, including anomalies observed in patients carrying TBC1D1 mutations, was found in kidneys of some Tbc1d1 (-/-) mice. Significantly reduced Glut4 levels were detected in kidneys of Tbc1d1 (-/-) mice and the dysplastic kidney of a TBC1D1 mutation carrier versus controls. TBC1D1 and SLC2A4 encoding GLUT4 were highly expressed in human fetal kidney. These data demonstrate heterozygous deactivating TBC1D1 mutations in CAKUT patients with a similar renal and ureteral phenotype, and provide evidence that TBC1D1 mutations may contribute to CAKUT pathogenesis, possibly via a role in glucose homeostasis. Sources: Literature |
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| Fetal anomalies v0.3510 | THRA | Zornitza Stark edited their review of gene: THRA: Changed publications: 22168587, 22494134, 25670821 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3510 | THRA | Zornitza Stark Marked gene: THRA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3510 | THRA | Zornitza Stark Gene: thra has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3510 | THRA | Zornitza Stark Phenotypes for gene: THRA were changed from HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6 to Hypothyroidism, congenital, nongoitrous, 6, MIM# 614450 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3509 | THRA | Zornitza Stark Publications for gene: THRA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3508 | THRA | Zornitza Stark Mode of inheritance for gene: THRA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3507 | THRA | Zornitza Stark reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypothyroidism, congenital, nongoitrous, 6, MIM# 614450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3502 | SLIT2 |
Krithika Murali gene: SLIT2 was added gene: SLIT2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SLIT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLIT2 were set to 26026792; 15130495 Phenotypes for gene: SLIT2 were set to CAKUT; vesicoureteric reflux Review for gene: SLIT2 was set to AMBER Added comment: PMID 26026792 Hwang et al 2019 - identified three unrelated individuals with CAKUT and different heterozygous SLIT2 missense mutations. - 1 patient presented with multiple bilateral subcortical renal cysts - 1 patient presented with multicystic dysplastic kidneys - 1 patient had right renal agenesis Authors provide supportive variant-specific mouse models. PMID: 34059960 Liu et al 2021 - 3 unrelated children from a Chinese Kidney Disease Database with vesicoureteric reflux had SLIT3 VUS identified PMID 19350278 Zu et al 2009 - x2 unrelated individuals with SLIT2 variants - not segregating with disease in either family Sources: Literature |
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| Fetal anomalies v0.3502 | NEK9 | Zornitza Stark Phenotypes for gene: NEK9 were changed from Arthrogryposis, Perthes disease, and upward gaze palsy, MONDO:0013660; NEK9-related lethal skeletal dysplasia, MONDO:0014870; Lethal congenital contracture syndrome 10, OMIM:617022; ?Arthrogryposis, Perthes disease, and upward gaze palsy, OMIM:614262 to Arthrogryposis, Perthes disease, and upward gaze palsy, MONDO:0013660; NEK9-related lethal skeletal dysplasia, MONDO:0014870; Lethal congenital contracture syndrome 10, OMIM:617022; Arthrogryposis, Perthes disease, and upward gaze palsy, OMIM:614262 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3501 | NEK8 | Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MONDO:0014174; Renal-hepatic-pancreatic dysplasia 2, OMIM:615415; ?Nephronophthisis 9, OMIM:613824; Nephronophthisis 9, MONDO:0013444 to Renal-hepatic-pancreatic dysplasia 2, MONDO:0014174; Renal-hepatic-pancreatic dysplasia 2, OMIM:615415; Nephronophthisis 9, OMIM:613824; Nephronophthisis 9, MONDO:0013444 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3413 | COQ7 |
Krithika Murali gene: COQ7 was added gene: COQ7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ7 were set to 33215859; 28125198; 31240163; 28409910; 26084283 Phenotypes for gene: COQ7 were set to Coenzyme Q10 deficiency, primary, 8 - MIM#616733 Review for gene: COQ7 was set to GREEN Added comment: Biallelic variants associated with primary coenzyme Q10 (CoQ10) deficiency, a heterogeneous multi-system disorder including early-postnatal features such as neonatal encephalopathy, contractures. Antenatal features reported include IUGR, oligohydramnios, feetal lung hypoplasia, dysplastic kidneys. Specifically for COQ7-related CoQ10 deficiency: PMID 33215859 Hashemi et al 2020 - report two affected individuals from a consanguineous Iranian family with homozygous COQ7 variants progressive spastic paraparesis diagnosed at age 1.5-2 with normal antenatal history. PMID 31240163 Kwong et al 2019 - report a patient with compound hetereozygous COQ7 variants, encephalo‐myo‐nephro‐cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ10 level. The proband was a DCDA twin, noted to have IUGR, oligohydramnios, cardiomegaly and tricuspid regurgitation antenatally. PMID 28409910 Wang et al 2017 - no antenatal features reported in their proband PMID 26084283 Freyer et al 2015 - report x1 patient with homozygous COQ7 variant. The pregnancy was complicated by oligohydramniosis, fetal lung hypoplasia and growth retardation. Sources: Literature |
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| Fetal anomalies v0.3400 | LTBP1 |
Krithika Murali gene: LTBP1 was added gene: LTBP1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LTBP1 were set to 33991472 Phenotypes for gene: LTBP1 were set to Cutis laxa, autosomal recessive, type IIE - MIM#619451 Review for gene: LTBP1 was set to GREEN Added comment: Homozygous premature truncating LTBP1 variants in eight affected individuals from four unrelated consanguineous families reported associated with autosomal recessive cutis laxa type IIE. Phenotypic features relevant in the prenatal setting include: - Congenital diaphragmatic hernia (1 individual) - Cleft palate (2 individuals) - Congenital heart defects - Renal anomalies (1 individual) - Microretrognathia (1 individual) - Hydrocephalus (1 individual) - Skeletal anomalies (craniosynostosis, short stature, brachydactyly, and syndactyly). Supportive patient-derived fibroblast and zebrafish studies. Sources: Literature |
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| Fetal anomalies v0.3380 | MN1 |
Zornitza Stark changed review comment from: Over 20 individuals described with de novo truncating variants in this gene; these cluster in the C-terminal and the authors postulate that that syndrome is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein. Sources: Literature; to: Over 20 individuals described with de novo truncating variants in this gene; these cluster in the C-terminal and the authors postulate that that syndrome is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein. Diaphragmatic hernia, craniosynostosis and brain abnormalities reported. Sources: Literature |
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| Fetal anomalies v0.3362 | LONP1 | Zornitza Stark changed review comment from: At least three unrelated cases described in the literature, ID is part of the phenotype.; to: At least three unrelated cases described in the literature, multiple congenital anomalies are part of the phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3359 | LIPT2 |
Zornitza Stark changed review comment from: Three individuals from two unrelated families; profound ID. Sources: Expert list; to: Three individuals from two unrelated families; onset is typically post-natal, though brain abnormalities reported in some. Sources: Expert list |
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| Fetal anomalies v0.3353 | LIAS | Zornitza Stark changed review comment from: At least three families reported, severe ID is part of the phenotype.; to: At least three families reported, clinical presentation is typically post-natal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3330 | NHP2 | Zornitza Stark Phenotypes for gene: NHP2 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 2 to Dyskeratosis congenita, autosomal recessive 2, MIM# 613987; Høyeraal-Hreidarsson syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3327 | NHP2 | Zornitza Stark changed review comment from: Three individuals reported altogether, of those two had DD/ID.; to: Three individuals reported altogether, one of whom had the more severe HH phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3317 | KDM1A |
Zornitza Stark changed review comment from: Three unrelated individuals with de novo missense variants in this gene and a neurodevelopmental phenotype. Note one of the individuals also had a de novo indel in ANKRD11. Some data published subsequently demonstrating functional impact of all three variants.; to: Three unrelated individuals with de novo missense variants in this gene and a neurodevelopmental phenotype. Note one of the individuals also had a de novo indel in ANKRD11. Some data published subsequently demonstrating functional impact of all three variants. LGA, cleft palate, brain abnormalities reported. |
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| Fetal anomalies v0.3313 | KCNQ5 |
Zornitza Stark changed review comment from: Four unrelated individuals reported with de novo missense variants in this gene and a neurodevelopmental disorder, including epileptic encephalopathy in some. Three of the variants demonstrated to be LoF and one GoF. Further individual reported in PMID 30359776 with mild ID and absence epilepsy and an intragenic duplication causing likely LoF.; to: Four unrelated individuals reported with de novo missense variants in this gene and a neurodevelopmental disorder, including epileptic encephalopathy in some. Three of the variants demonstrated to be LoF and one GoF. Further individual reported in PMID 30359776 with mild ID and absence epilepsy and an intragenic duplication causing likely LoF. Clinical presentation is typically post-natal. |
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| Fetal anomalies v0.3290 | CTNS | Zornitza Stark Phenotypes for gene: CTNS were changed from CYSTINOSIS NEPHROPATHIC TYPE; CYSTINOSIS LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE; CYSTINOSIS ADULT NON-NEPHROPATHIC TYPE to Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900; Cystinosis, nephropathic MIM#219800; Cystinosis, ocular nonnephropathic MIM#219750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3279 | CTNS | Belinda Chong reviewed gene: CTNS: Rating: RED; Mode of pathogenicity: None; Publications: 32564281, 20301574, 9537412, 31068690; Phenotypes: Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900, Cystinosis, nephropathic MIM#219800, Cystinosis, ocular nonnephropathic MIM#219750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3279 | ZBTB24 |
Krithika Murali gene: ZBTB24 was added gene: ZBTB24 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZBTB24 were set to 32865561; 21596365; 29023266; 32061411; 21906047; 28128455; 23739126; 22786748 Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 - MIM#614069 Review for gene: ZBTB24 was set to GREEN Added comment: Well reported association with ICF2 (immunodeficiency-centromeric instability facial anomalies syndrome 2). Patients have immunodeficiency (mainly hypo/agammaglobulinemia in the presence of B cells), recurrent infections (namely respiratory and gastrointestinal) and dysmorphic facies. Although antenatal features not thoroughly described for published cases, low birth weight has been a reported feature as well as hypertelorism and micrognathia/retrognathia - these have the potential to be detected prenatally. PMID 32865561 Helfricht et al 2020 - "loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance". PMID 32061411 Banday. et al 2020 - report a patient with this condition and granulomatous hepatitis. Review phenotype of previously reported patients, low birth weight and facial dysmorphism including micrognathia noted in other cases. PMID 29023266 Conrad et al 2017 - describe a 17 month old boy with recurrent infections, growth failure, facial anomalies (including hyperterlorism/low set ears), and inflammatory bowel disease. No antenatal information. PMID 28128455 van den Boogaard 2017 - 5 new patients described PMID 23739126 Nitta et al 2013 - report 3 unrelated patients, x1 patient - lower birth weight and head circumference. At age 5 had macrocephaly, hyperterlorism. Noted to have bilateral hydronephrosis. x1 patient BW 2660g, micrognathia, hyperterlorism. PMID 21906047 Chouery et al 2012 - 3 siblings from a Lebanese family with novel homozygous LoF variant. Apparently normal pregnancies, at time of diagnostic assessment HC between the 5th and 15th centiles, height below the 5th percentile. Dysmorphic features including high arched palate, small chin, retrognathism and everted lower lips. PMID 22786748 Cerbone et al 2012 - report an 8 year old M of consanguineous Moroccan ancestry with ID, dysmorphic features, cafe au last macules and a large arachnoid cyst in the right temporal region, causing compression of the temporal lobe and lateral ventricle PMID 21596365 de Greef et al 2011 - report 4 new unrelated patients, no antenatal information Sources: Literature |
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| Fetal anomalies v0.3254 | HESX1 | Zornitza Stark changed review comment from: Variants in this gene are associated with a spectrum of abnormalities: isolated pituitary deficiency through to septo-optic dysplasia. Optic nerve hypoplasia reported as part of this rather than AMC.; to: Variants in this gene are associated with a spectrum of abnormalities including corpus callosum abnormalities and hand abnormalities. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3238 | GPAA1 |
Zornitza Stark changed review comment from: At least 5 unrelated families reported with bi-allelic variants in this gene and delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.; to: At least 5 unrelated families reported with bi-allelic variants in this gene and delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. Clinical presentation is typically post-natal. |
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| Fetal anomalies v0.3221 | GMNN |
Zornitza Stark changed review comment from: Two of the three reported individuals had ID. Sources: Expert list; to: IUGR is a key feature. Sources: Expert list |
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| Fetal anomalies v0.3221 | GLIS2 | Zornitza Stark Phenotypes for gene: GLIS2 were changed from NEPHRONOPHTHISIS 7 to Nephronophthisis 7, OMIM#611498; MONDO:0012680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3217 | GALNT2 |
Zornitza Stark changed review comment from: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. Sources: Literature; to: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. Microcephaly and poor growth but age of onset of these features is uncertain. Sources: Literature |
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| Fetal anomalies v0.3205 | FUT8 |
Zornitza Stark changed review comment from: Three unrelated individuals reported with bi-allelic variants in this gene. Sources: Expert list; to: Three unrelated individuals reported with bi-allelic variants in this gene. IUGR and congenital anomalies reported. Sources: Expert list |
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| Fetal anomalies v0.3151 | LRRC32 |
Krithika Murali gene: LRRC32 was added gene: LRRC32 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC32 were set to 30976112 Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay - MIM#619074 Review for gene: LRRC32 was set to AMBER Added comment: Gene previously reviewed for PanelApp Feb 2021 - no new relevant publications since -- Three individuals from two consanguineous families with cleft palate, proliferative retinopathy, and developmental delay had the same homozygous biallelic variant, c.1630C>T; p.(Arg544Ter), segregated and shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death. Sources: Literature |
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| Fetal anomalies v0.3151 | LRP6 |
Krithika Murali gene: LRP6 was added gene: LRP6 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LRP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LRP6 were set to 16126904; 30950205; 26387593; 26963285; 28813618; 29500247; 33164649; 34306029 Phenotypes for gene: LRP6 were set to Tooth agenesis, selective, 7 - MIM#616724; cleft lip/palate Review for gene: LRP6 was set to AMBER Added comment: LoF variants known to be associated with tooth agenesis. In addition, x2 unrelated families from 2 different studies with heterozygous LRP6 variant had tooth agenesis and cleft lip/palate (PMID 29500247; 26963285). Growth failure reported in some individuals but unclear if prenatal in onset (PMID 26963285). Minor finger/ear anomalies reported in x2 patients (PMID 26387593; 30950205)- unlikely to be detected antenatally and one of the reported patients (30950205) had x2 chromosome deletions, one of which involved LRP6 and multiple other genes. --- PMID: 34306029 Huang et al 2021 - Heterozygous LRP6: c.2570G > A (p.R857H), harbored by six members of a Chinese family, including 4 with tooth agenesis. Sparse hair another phenotypic feature. PMID: 33164649 Yu et al 2021 - identified 4 novel LRP6 heterozygous mutations in 4 of 77 oligodontia patients. One patient with a nonsense paternally inherited variant had a hypohidrotic ectodermal dysplasia phenotype - no antenatal features, father had oligodontia. Supportive functional evidence PMID: 29500247 Basha et al 2018 - Nonsense LRP6 variant identified in a family with cleft lip/palate. Proband had bilateral cleft lip and palate with missing upper lateral incisors, mother had bilateral cleft lip. x1 unaffected brother but family members not reassessed for oligodontia after variant identified. PMID: 28813618 Dinckan et al 2018 - heterozygous splice site LRP6 variant identified in 1 family with isolated tooth agenesis. Affected family members also had mild periocular hyperpigmentation and hypoplastic alae nasi - thought to be unrelated to phenotype PMID: 26963285 Ockeloen et al 2016 - frameshift variant identified in patient with tooth agenesis and orofacial clefting - boy born with bilateral cleft lip, L) sided cleft of the alveolus and complete cleft of the hard and soft palate. Also noted to have growth retardation, hypermetropia and small median alveolar manibular cleft. Maternal relatives with variant had severe tooth agenesis but no clefting. Canonical splice site variant identified in a patient with isolated severe tooth agenesis. Targeted resequencing showed statistically significant enrichment of unique LRP6 variants in tooth agenesis patients (7/67 versus 13/706 controls), not orofacial clefting cohort. 4/7 of these patients required growth hormone therapy and 3/7 had clinodactyly in addition to dental anomalies. PMID: 26387593 – Massink et al 2015 - x4 LoF heterozygous LRP6 variants identified in 4 unrelated families with isolated severe tooth agenesis. All affected members of one family showed minor anatomical variation of the ear and underdevelopment of the thumb PMID: 30950205 Ross et al 2019 - Proband with oligodontia and thrombocytopenia, also had mild finger and ear anomalies. Array revealed an interstitial loss of 150 kb in 8p23.1 encompassing MCPH1 and ANGPT2 and an interstitial loss of 290 kb in 12p13.2 encompassing ETV6, BCL2L14 and LRP6. Sources: Literature |
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| Fetal anomalies v0.3148 | COL25A1 |
Zornitza Stark gene: COL25A1 was added gene: COL25A1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COL25A1 were set to 35077597; 26437029 Phenotypes for gene: COL25A1 were set to Arthrogryposis multiplex congenita MONDO:0015168 Review for gene: COL25A1 was set to GREEN Added comment: 6 cases from 4 unrelated families with AMC as a feature of the phenotype PMID: 35077597 - 5 patients from 3 unrelated families with biallelic missense and splice site COL25A1 variants presenting with arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype PMID: 26437029 - Patient: 273182 in DECIPHER with compound het missense variants. Phenotype includes Congenital finger flexion contractures, Contracture of the distal interphalangeal joint of the 2nd finger, Duane anomaly Sources: Literature |
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| Fetal anomalies v0.3140 | ESRP2 |
Krithika Murali gene: ESRP2 was added gene: ESRP2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ESRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ESRP2 were set to 29805042 Phenotypes for gene: ESRP2 were set to Cleft lip Review for gene: ESRP2 was set to AMBER Added comment: No new publications since last PanelApp review Feb 2021 -- PMID: 29805042 Cox et al. Identified ESRP2 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr16:g.68266284C>T;p.Arg315) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant (chr16:g.68265234G>A;p.Arg520*) in another family. Sources: Literature |
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| Fetal anomalies v0.3096 | PPP3CA | Zornitza Stark Phenotypes for gene: PPP3CA were changed from Severe Neurodevelopmental Disease with Seizures to Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3094 | PPP3CA | Zornitza Stark reviewed gene: PPP3CA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3031 | PPP3CA | Belinda Chong reviewed gene: PPP3CA: Rating: AMBER; Mode of pathogenicity: None; Publications: 29432562, 28942967, 28942967; Phenotypes: Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265, Developmental and epileptic encephalopathy 91 617711; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3020 | PIK3C2A |
Zornitza Stark changed review comment from: Three unrelated families, ID is part of the phenotype. Sources: Expert list; to: Three unrelated families, cataracts and skeletal abnormalities are part of the phenotype. Sources: Expert list |
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| Fetal anomalies v0.2993 | PDE6D |
Krithika Murali gene: PDE6D was added gene: PDE6D was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PDE6D was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE6D were set to 30423442; 24166846 Phenotypes for gene: PDE6D were set to Joubert syndrome 22 - MIM#615665 Review for gene: PDE6D was set to GREEN Added comment: Biallelic variants associated with Joubert syndrome identified in 2 families. Antenatal detection possible. 30423442 Megarbane et al 2018 Report homozygous truncating PDE6D variant in a male infant with post-axial polydactyly noted at birth on all extremities. Brain MRI at 6 months of age showed cerebellar vermis agenesis, hypoplastic corpus callosum, cortical atrophy of the temporal lobes and molar tooth sign. PMID 24166846 Thomas et al 2014 report a consanguineous family with three affected and 2 healthy sibs. Features noted in both liveborn children: - 1/2 IUGR - 1/2 facial dysmorphism - 2/2 postaxial polydactyly - 1/2 syndactyly - 1/2 renal hypoplasia - 2/2 microphthalmia - 1/2 supportive MRI-B features - 1/2 coloboma 3rd sibling is a male fetus terminated at 14 weeks gestation following findings of brain anomalies and polydactyly. Supportive animal models Sources: Literature |
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| Fetal anomalies v0.2993 | NPM1 |
Krithika Murali gene: NPM1 was added gene: NPM1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NPM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NPM1 were set to 31570891 Phenotypes for gene: NPM1 were set to Dyskeratosis congenita Review for gene: NPM1 was set to AMBER Added comment: Heterozygous variants identified in 2 patients with dyskeratosis congenita (DKC). x1 patient with NPM1 missense mutation presented with severe growth defects at birth, thumb abnormalities and thrombocytopenia. x1 patient with in-frame NPM1 deletion presented with skin pigmentation abnormalities, nail dystrophy, microcephaly, developmental delay, short stature, skeletal abnormalities in the radius and bone marrow failure by age 6. Some of these features may be amenable to antenatal detection. Sources: Literature |
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| Fetal anomalies v0.2957 | NTRK2 |
Zornitza Stark changed review comment from: Three unrelated individuals reported with this phenotype. Note recurrent missense in this gene also causes EE. Sources: Expert list; to: Clinical presentation for both disorders is typically post-natal. Sources: Expert list |
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| Fetal anomalies v0.2951 | G6PD |
Krithika Murali gene: G6PD was added gene: G6PD was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: G6PD 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: G6PD were set to 1316704; 26279483; 18177777; 17825683; 1127504; 7472841 Phenotypes for gene: G6PD were set to Haemolytic anaemia, G6PD deficient (300908) Review for gene: G6PD was set to AMBER Added comment: Well-known association with G6PD deficiency. Borderline red-amber gene for fetal anomalies. However, as features of anaemia can sometimes be detected in fetus antenatally and therapeutic/maternal trigger avoidance options available, I have favoured amber rating. PMID: 26279483 Keller et al 2015 - report a mother who is a carrier for a G6PD variant (Guadalajara variant) with a family history of a brother and paternal uncle who died as neonates from severe hydrops. She was counselled to avoid substances that could precipitate oxidative stress from 22 weeks gestation onwards. During her first pregnancy, a male fetus was found to have mild cardiomegaly at 31 weeks with elevated MCAPSV - suggestive of anaemia. Intrauterine transfusion instituted. Presence of maternally inherited G6PD variant confirmed in the fetus. There are other case reports of hydrops fetalis presumed secondary to G6PD deficiency but evidence is limited.. 4999390; 1127504 - older studies, no genomic confirmation available. 4999390 Perkins et al 1971 - Mother presumed to be a carrier for G6PD deficiency and all 3 babies presumed to have the same - 1st child neonatal jaundice with abnormal G6PD test result and death at 59 days of life from undetermined cause - 2nd pregnancy - mother given sulfizoxazole for UTI during pregnancy, delivered stillborn infant at 36 weeks with hydrops fetalis and severe anaemia - 3rd child - well, neonatal jaundice and abnormal G6PD test. Mother O neg blood group, all three babies +ve blood group, DAT -ve and RhoGam given each pregnancy. 1127504 - Mentzer and Collier et al 1975 Male infant died at 2 hours of life with evidence of haemolysis and autopsy findings of hydrops. G6PD screening test in baby abnormal. Mother had low-normal G6PD activity, abnormal ascorbate cyanide test, abnormal MTT cytochemical however no abnormal migrating band of G6PD activity was present on electrophoresis. URTI episode during pregnancy, ascorbic acid consumption and fava bean consumption noted. G6PD deficiency presumed in mother and infant but not genomically confirmed. 23719252; 24999569 - Two case reports identified. However, a second diagnosis was present in both and the G6PD deficiency may have contributed to severity rather than being the primary factor. Sources: Literature |
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| Fetal anomalies v0.2951 | MYBPC1 | Alison Yeung Phenotypes for gene: MYBPC1 were changed from Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4 614915 to Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4, MIM# 614915 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2950 | MYBPC1 | Alison Yeung reviewed gene: MYBPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 1B, MIM# 614335, Lethal congenital contracture syndrome 4, MIM# 614915; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2907 | SMG9 |
Zornitza Stark changed review comment from: Three unrelated families reported, severe congenital malformation syndrome, ID is part of the phenotype in survivors. Sources: Expert list; to: Three unrelated families reported, severe congenital malformation syndrome. Sources: Expert list |
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| Fetal anomalies v0.2892 | UROS |
Krithika Murali gene: UROS was added gene: UROS was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UROS were set to 34187847; 34828434; 15065102 Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic - MIM#263700; hydrops fetalis; multiple congenital anomalies Review for gene: UROS was set to GREEN Added comment: Biallelic variants associated with congenital erytropoietic porphyria (CEP). PMID 34187847 Khalouaoui A et al 2021 report one infant with CEP secondary to homozygous UROS variants. Prenatal ultrasound at 25 weeks of gestation revealed an increased nuchal translucency and myocardial hypertrophy. PMID: 34828434 Arnaud et al 2021 - report one fetus miscarried in the 2nd trimester with 22 weeks ultrasound showing hyperechogenic small intestine with short femurs. Subsequent pregnancy MTOP after antenatal USS showed hygroma coli, ascites, short femurs, double outlet right ventricle. Genomic sequencing on stored fetal DNA samples confirmed homozygous UROS p.Cys73Arg variants in both fetuses. PMID 15065102 Lazebnik et al 2004 reported the prenatal findings of two siblings with CEP secondary to homozygous pathogenic C73R variants. 1st child - USS at 17.5 weeks gestation showed increased nuchal thickness (9.7mm) with mild ascites, pericardial effusion, and skin oedema which persisted on subsequent scans. 2nd child - 16 week USS showed increased nuchal thickness (8.7mm) with scalp oedema, ascites, pericardial effusion, skin oedema and hepatomegaly. Other cases with antenatal features, particularly non-immune hydrops, secondary to suspected CEP reported but not confirmed molecularly. Sources: Literature |
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| Fetal anomalies v0.2892 | LAMB2 |
Krithika Murali gene: LAMB2 was added gene: LAMB2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LAMB2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LAMB2 were set to 16450351 Phenotypes for gene: LAMB2 were set to Pierson syndrome-MIM#609049; Nephrotic syndrome, type 5, with or without ocular abnormalities-MIM#614199 Review for gene: LAMB2 was set to AMBER Added comment: Biallelic variants associated with Pierson syndrome. Phenotypic features include congenital nephrotic syndrome, ocular anomalies including microcoria. Most affected individuals die early from renal disease with survivors tending to have ID/visual loss. Prenatal features reported in 1 consanguineous Turkish family with 4 pregnancies affected by Pierson syndrome. Antenatal ultrasound features noted include: - 2/4 homogenous hyperechogenicity of the kidneys similar to bone tissue - 2/4 enlargement of fetal kidneys - 2/4 bilateral pyelectasis - 1/4 oligohydramnios --> anhydramnios - 1/4 hydrops - 1/4 ancencephaly All 4 fetuses had ultrasound anomalies. Anencephaly seen in the 4th pregnancy noted at 11 weeks resulting in MTOP. Homozygosity for LAMB2 variant confirmed. PM showed that kidneys were appropriate for gestational age. I could not find another case report of anencephaly with Pierson syndrome, this may be an incidental finding. Sources: Literature |
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| Fetal anomalies v0.2891 | FLNC | Zornitza Stark Phenotypes for gene: FLNC were changed from Arthrogryposis; congenital myopathy; Cardiomyopathy, familial restrictive 5 - MIM #617047; Cardiomyopathy, familial hypertrophic, 26 -MIM# 617047; Myopathy, distal, 4 - #614065; Myopathy, myofibrillar, 5 - MIM#609524 to Arthrogryposis; congenital myopathy; Myopathy, myofibrillar, 5 - MIM#609524 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2849 | HS2ST1 |
Krithika Murali gene: HS2ST1 was added gene: HS2ST1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HS2ST1 were set to 33159882 Phenotypes for gene: HS2ST1 were set to Neurofacioskeletal syndrome with or without renal agenesis-MIM#619194; multiple congenital anomalies; arthrogryposis Review for gene: HS2ST1 was set to GREEN Added comment: PMID 33159882 - Scheenberger et al 2020 Biallelic HS2ST1 variants associated with disease reported in 4 affected individuals from 3 unrelated families, including one affected fetus with arthrogryposis, skeletal anomalies, bilateral renal agenesis. Other congenital anomalies reported include agenesis or hypoplasia of the corpus callosum. Sources: Literature |
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| Fetal anomalies v0.2846 | FLNC |
Krithika Murali changed review comment from: ClinGen definitive gene-disease validation for myofibrillar myopathy type 5 and dilated cardiomyopathy. Predominantly adult onset phenotype, AD inheritance. 4 unrelated cases with likely de novo FLNC variants presenting with congenital myopathy and arthrogryposis have also been reported which are features amenable to antenatal detection. PMID 29858533 Kiselev et al reported 4 unrelated patients with early onset myopathy and restrictive cardiomyopathy. 3/4 also presented with arthrogryposis. x1 patient required delivery via CS due to breech presentation and at birth was noted to have arthrogryposis and hip dysplasia - de novo FLNC variant confirmed. RCM diagnosed age 2 x1 patient noted to have IUGR in a pregnancy complicated by pre-eclampsia. At birth was noted to have arthrogryposis, hip subluxation and abdominal wall weakness with herniation. RCM diagnosed age 6 months. Variant not present in unaffected mother, paternal DNA unavailable. x1 patient required CS delivery due to insufficient rotation in birth canal. Noted to have arthrogryposis at birth. Variant confirmed to be de novo x1 patient presented with muscle weakness first year of life, RCM age 3. Parents declined genetic testing. --- Other cases of interest PMID 30260051 Schubert et al 2018 - report two restrictive cardiomyopathy families with childhood onset disease with age 1 being the earliest age of diagnosis in a DCDA monozygotic twin who was also diagnosed with a small VSD perinatally. Both twins were also noted to have extra-cardiac manifestations at the time of diagnosis including developmental delay, hypotonia, dysmorphic facial features, and clasped thumbs with onset of kidney dysfunction age 3 post-cardiac transplant. PMID: 32516863 – Kolbel et al 2020 report one neonate with homozygous FLNC variant c.1325C>G (p.Pro442Arg). Absent from gnomad. Presented with weak suck first month of life with subsequent motor development delay, generalised muscular hypotonia, contractures. Variant confirmed in both unaffected parents. Authors postulate this is a novel case of homozygous FLNC variants associated with congenital presentation. This is a single case report, only heterozygous variants reported so far including in congenital presentations, both parents with het variants unaffected. Possibility of an alternative genetic explanation for this patient's presentation not excluded. Sources: Literature; to: ClinGen definitive gene-disease validation for myofibrillar myopathy type 5 and dilated cardiomyopathy. Predominantly adult onset phenotype, AD inheritance. 4 unrelated cases with likely de novo FLNC variants presenting with congenital myopathy and arthrogryposis have also been reported. These features/complications of these features are amenable to antenatal detection. PMID 29858533 Kiselev et al reported 4 unrelated patients with early onset myopathy and restrictive cardiomyopathy. 3/4 also presented with arthrogryposis. x1 patient required delivery via CS due to breech presentation and at birth was noted to have arthrogryposis and hip dysplasia - de novo FLNC variant confirmed. RCM diagnosed age 2 x1 patient noted to have IUGR in a pregnancy complicated by pre-eclampsia. At birth was noted to have arthrogryposis, hip subluxation and abdominal wall weakness with herniation. RCM diagnosed age 6 months. Variant not present in unaffected mother, paternal DNA unavailable. x1 patient required CS delivery due to insufficient rotation in birth canal. Noted to have arthrogryposis at birth. Variant confirmed to be de novo x1 patient presented with muscle weakness first year of life, RCM age 3. Parents declined genetic testing. --- Other cases of interest PMID 30260051 Schubert et al 2018 - report two restrictive cardiomyopathy families with childhood onset disease with age 1 being the earliest age of diagnosis in a DCDA monozygotic twin who was also diagnosed with a small VSD perinatally. Both twins were also noted to have extra-cardiac manifestations at the time of diagnosis including developmental delay, hypotonia, dysmorphic facial features, and clasped thumbs with onset of kidney dysfunction age 3 post-cardiac transplant. PMID: 32516863 – Kolbel et al 2020 report one neonate with homozygous FLNC variant c.1325C>G (p.Pro442Arg). Absent from gnomad. Presented with weak suck first month of life with subsequent motor development delay, generalised muscular hypotonia, contractures. Variant confirmed in both unaffected parents. Authors postulate this is a novel case of homozygous FLNC variants associated with congenital presentation. This is a single case report, only heterozygous variants reported so far including in congenital presentations, both parents with het variants unaffected. Possibility of an alternative genetic explanation for this patient's presentation not excluded. Sources: Literature |
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| Fetal anomalies v0.2846 | FLNC |
Krithika Murali gene: FLNC was added gene: FLNC was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FLNC were set to 29858533; 30260051; 32516863 Phenotypes for gene: FLNC were set to Arthrogryposis; congenital myopathy; Cardiomyopathy, familial restrictive 5 - MIM #617047; Cardiomyopathy, familial hypertrophic, 26 -MIM# 617047; Myopathy, distal, 4 - #614065; Myopathy, myofibrillar, 5 - MIM#609524 Review for gene: FLNC was set to GREEN Added comment: ClinGen definitive gene-disease validation for myofibrillar myopathy type 5 and dilated cardiomyopathy. Predominantly adult onset phenotype, AD inheritance. 4 unrelated cases with likely de novo FLNC variants presenting with congenital myopathy and arthrogryposis have also been reported which are features amenable to antenatal detection. PMID 29858533 Kiselev et al reported 4 unrelated patients with early onset myopathy and restrictive cardiomyopathy. 3/4 also presented with arthrogryposis. x1 patient required delivery via CS due to breech presentation and at birth was noted to have arthrogryposis and hip dysplasia - de novo FLNC variant confirmed. RCM diagnosed age 2 x1 patient noted to have IUGR in a pregnancy complicated by pre-eclampsia. At birth was noted to have arthrogryposis, hip subluxation and abdominal wall weakness with herniation. RCM diagnosed age 6 months. Variant not present in unaffected mother, paternal DNA unavailable. x1 patient required CS delivery due to insufficient rotation in birth canal. Noted to have arthrogryposis at birth. Variant confirmed to be de novo x1 patient presented with muscle weakness first year of life, RCM age 3. Parents declined genetic testing. --- Other cases of interest PMID 30260051 Schubert et al 2018 - report two restrictive cardiomyopathy families with childhood onset disease with age 1 being the earliest age of diagnosis in a DCDA monozygotic twin who was also diagnosed with a small VSD perinatally. Both twins were also noted to have extra-cardiac manifestations at the time of diagnosis including developmental delay, hypotonia, dysmorphic facial features, and clasped thumbs with onset of kidney dysfunction age 3 post-cardiac transplant. PMID: 32516863 – Kolbel et al 2020 report one neonate with homozygous FLNC variant c.1325C>G (p.Pro442Arg). Absent from gnomad. Presented with weak suck first month of life with subsequent motor development delay, generalised muscular hypotonia, contractures. Variant confirmed in both unaffected parents. Authors postulate this is a novel case of homozygous FLNC variants associated with congenital presentation. This is a single case report, only heterozygous variants reported so far including in congenital presentations, both parents with het variants unaffected. Possibility of an alternative genetic explanation for this patient's presentation not excluded. Sources: Literature |
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| Fetal anomalies v0.2838 | TNNI2 | Zornitza Stark Phenotypes for gene: TNNI2 were changed from Arthrogryposis multiplex congenita, distal, type 2B 601680 to Arthrogryposis multiplex congenita, distal, type 2B MIM#601680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2832 | ACAN | Zornitza Stark Phenotypes for gene: ACAN were changed from SPONDYLOEPIMETAPHYSEAL DYSPLASIA AGGRECAN TYPE; SPONDYLOEPIPHYSEAL DYSPLASIA TYPE KIMBERLEY to Spondyloepimetaphyseal dysplasia, aggrecan type, OMIM# 612813; Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2825 | KIF26B |
Zornitza Stark gene: KIF26B was added gene: KIF26B was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF26B were set to 30151950 Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis Review for gene: KIF26B was set to RED Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Sources: Expert Review |
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| Fetal anomalies v0.2823 | ACAN | Alison Yeung reviewed gene: ACAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24762113, 27870580, 19110214, 30124491, 28331218, 20137779; Phenotypes: Spondyloepimetaphyseal dysplasia, aggrecan type, OMIM# 612813, Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2818 | SLC35A1 | Zornitza Stark changed review comment from: Three unrelated families reported.; to: Three unrelated families reported, variable severity, including onset. Microcephaly reported, but onset uncertain. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2785 | MAGEL2 | Zornitza Stark Phenotypes for gene: MAGEL2 were changed from ARTHROGRYPOSIS MULTIPLEX CONGENITA; Schaaf-Yang syndrome, 615547; Schaaf-Yang syndrome to Schaaf-Yang syndrome, MIM# 615547 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2766 | LMX1B |
Zornitza Stark changed review comment from: Nail-patella syndrome (NPS) is an autosomal-dominant disease characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Varying degrees of proteinuria or hematuria are present, and can occasionally progress to chronic renal failure. >300 families reported.; to: Nail-patella syndrome (NPS) is an autosomal-dominant disease characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Varying degrees of proteinuria or hematuria are present, and can occasionally progress to chronic renal failure. >300 families reported. Prenatal presentations with abnormal limb movement reported. |
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| Fetal anomalies v0.2756 | ERGIC1 |
Krithika Murali gene: ERGIC1 was added gene: ERGIC1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERGIC1 were set to 28317099; 34037256; 31230720 Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100 Review for gene: ERGIC1 was set to GREEN Added comment: Recent Panelapp review by Z. Stark Oct 2021 - no new publications since --- Pehlivan et al. 2019 (PMID:31230720) identified the third case of arthrogryposis in a child who harboured a previously unreported homozygous variant (c.782G>A; p.Gly261Asp) in this gene. Parents were heterozygous carriers. Functional studies were not performed. Created: 14 Oct 2021, 7:23 a.m. | Last Modified: 14 Oct 2021, 7:23 a.m. Panel Version: 0.9373 Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi. Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents. Sources: Literature Sources: Literature |
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| Fetal anomalies v0.2756 | ERBB3 |
Krithika Murali gene: ERBB3 was added gene: ERBB3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ERBB3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERBB3 were set to 31752936; 17701904; 33720042 Phenotypes for gene: ERBB3 were set to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease (HSCR, aganglionic megacolon) MIM#142623 Review for gene: ERBB3 was set to GREEN Added comment: Biallelic variants associated with multi-system disorder, including gut dysmotility/Hirschsprung disease; with or without contractures. -- PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and other features of neurocristinopathy including short-segment HSCR, progressive axonal peripheral neuropathy, dysautonomia, hypopigmentation, deafness. Note variants in this gene have also recently been linked to Hirschsprung's disease. PMID 17701904: Lethal congenital contractual syndrome: Two families reported with contractures, positional approach used in gene discovery (2007). PMID 33720042 - Seven variants (missense and frameshfit) from four independent families with Hirschsprung disease (HSCR) reported. All reported individuals variably associated with conditions such as HSCR, chronic intestinal pseudo-obstruction, peripheral neuropathy, and arthrogryposis. Functional study revealed mutant proteins reduced protein expression or altered phosphorylation of the mutant receptors. Sources: Literature |
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| Fetal anomalies v0.2756 | INVS | Zornitza Stark Phenotypes for gene: INVS were changed from Nephronophthisis 2 602088 to Nephronophthisis 2, MIM# 602088 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2735 | HPGD | Zornitza Stark Phenotypes for gene: HPGD were changed from CRANIOOSTEOARTHROPATHY to Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100; Cranioosteoarthropathy MIM#259100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2727 | NMNAT2 | Zornitza Stark Phenotypes for gene: NMNAT2 were changed from hydropic placenta; hydrocephalus; micrognathia; bilateral hypoplastic lungs; hypoplastic cerebellum; severely reduced skeletal muscle mass or absence; cleft palate; hydrops fetalis; flexion contractures of all extremities; cystic hygroma to Hydrops fetalis and multiple fetal anomalies; polyneuropathy; erythromelalgia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2712 | HPGD | Ain Roesley reviewed gene: HPGD: Rating: RED; Mode of pathogenicity: None; Publications: 20406614, 32282352, 31878983, 29282707; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2712 | FAT1 |
Krithika Murali gene: FAT1 was added gene: FAT1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAT1 were set to 30862798; 26905694; 34202629; 34013115; 33418956; 32902815 Phenotypes for gene: FAT1 were set to multiple congenital anomalies; nephropathy; ocular anomalies; hand and foot anomalies Review for gene: FAT1 was set to GREEN Added comment: No OMIM gene-disease association, but multiple affected individuals from unrelated families reported with biallelic FAT1 variants and syndromic features consisting of ocular anomalies, hand/foot malformations and nephropathy. Although diagnosis antenatally not yet reported, some phenotypic features are detectable antenatally. PMID: 30862798 Larouchi et al 2019 - homozygous frameshift FAT1 variants identified in 10 affected individuals from 5 unrelated consanguineous families. The patients presented with syndromic features including ocular anomalies (ptosis, microphthalmia, coloboma, amblyopia), nephropathy (FSGS, proteinuria, haematuria), toe syndactyly and facial dysmorphism. Animal models showing that deletion of Fat1 leads to coloboma in mouse and zebrafish. PMID 26905694 Gee et al 2016 – report recessive mutations in FAT1 in four unrelated consanguineous families with a combination of steroid-resistant nephrotic syndrome, tubular ectasia, haematuria and variable neurodevelopmental findings such ID, polymicrogyria and hydrocephalus. X1 child with pulmonary stenosis. PMID: 34202629 Peluso et al 2021 – Homozygous FAT1 frameshift variant NM_005245.4:c.9729del identified in a child of consanguineous parents with bilateral anophthalmia and hand/foot malformations including - right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. Patient also had congenital heart defects including VSD, ASD and bicuspid aortic valve. Proband also had a microarray which detected a maternally inherited 350 kb 15q26.3 duplication including OMIM morbid gene CERS3 (AR condition) and part of the OMIM morbid gene ADAMTS17 (AR condition). Mother healthy, CNV unrelated to patient’s phenotype. PMID: 34013115 Fabretti et al 2021 – report 4 patients with biallelic FAT1 variants from 3 unrelated families with syndactyly, ophthalmologic and renal phenotype consistent with previously reported cases. PMID: 33418956 Haug et al 2021 - Genetic analysis showed that proband with phenotypic features consistent with other reported cases was compound heterozygous for a frameshift FAT1 variant and 1.8Mb 4q35.2 del including FAT1. PMID: 32902815 Rossanti et al 2021 – Biallelic FAT1 variants reported in a child with isolated mild proteinuria and no syndromic features Sources: Literature |
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| Fetal anomalies v0.2710 | NMNAT2 | Ain Roesley reviewed gene: NMNAT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31136762, 31132363, 25271157, 20126265; Phenotypes: Hydrops fetalis and multiple fetal anomalies, polyneuropathy, erythromelalgia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2710 | IGF2 | Zornitza Stark Phenotypes for gene: IGF2 were changed from BECKWITH-WIEDEMANN SYNDROME; CHROMOSOME 11P15.5-RELATED RUSSELL-SILVER SYNDROME to Growth restriction, severe, with distinctive facies, MIM#616489 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2616 | MECOM | Zornitza Stark Phenotypes for gene: MECOM were changed from Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 MIM#616738 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2597 | HAND2 |
Krithika Murali edited their review of gene: HAND2: Added comment: No OMIM gene disease association. Borderline red-amber gene. PMID: 26676105 Lu et al 2016 - 145 unrelated patients with CHD, Han Chinese descent versus 200 unrelated controls had HAND2 gene sequencing. In x1 patient with ToF hetrozygous HAND2 c.140T>C p.L47P variant identified, parents unaffected, variant reported to be de novo but paternity not confirmed. Absent from gnomad, x1 het synonymous variant in this position only. Functional analysis showed reduced transcriptional activity PMID: 32134193 Cohen et al 2020 - 31-month-old male with unicommissural unicuspid aortic valve, moderate aortic stenosis, and mild pulmonic stenosis. CMA identified 546kb deletion on chr 4q34.1 (174364195-174910239[GRCh37/hg19]). Deletion encompasses exons 1 and 2 of SCRG1, HAND2, and HAND2-AS1. Deletion paternally inherited - proband's father had history of ToF. Novel deletion - no similar deletions in Decipher or DGV. Proband also had CHD7 VUS (c.2830C>T, p.Arg944Cys) – but no features of CHARGE syndrome and CHD7 variant present in 7 hets in gnomad PMID: 30217752 Liu et al 2019 - screened 206 unrelated Han Chinese patients with adult-onset idiopathic DCM and 300 unrelated controls. Identified HAND2 variant c.199G>T; p.(Glu67*). Authors report segregation of the variant with other affected individuals in the family including x2 with VSD/PDA PMID: 26865696 Sun et al 2016 - HAND2 sequenced in 192 unrelated Han Chinese patient. Het p.S65I variant identified in a patient with VSD and present in all 7 family members with CHD and absent from 13 unaffected members. Variant present in gnomad – 3 hets (x1 East Asian, x1 South Asian, x1 Latin American) PMID 20819618 - Shen et al 2010 131 unrelated Han Chinese patients with ToF had HAND2 gene sequencing. Het c.32C>G p.Pro11Arg identified in x2 unrelated patients – no seg, not in gnomad but in area of low coverage. c.42C>T – present in x1 patient with ToF + VSD – no segregation data, not in gnomad but in area of low coverage; Changed rating: AMBER; Changed publications: 26865696, 32134193, 26676105, 30217752, 20819618 |
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| Fetal anomalies v0.2595 | SHROOM3 | Zornitza Stark Classified gene: SHROOM3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2595 | SHROOM3 | Zornitza Stark Gene: shroom3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2594 | SHROOM3 | Zornitza Stark reviewed gene: SHROOM3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2594 | SHROOM3 | Zornitza Stark Marked gene: SHROOM3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2594 | SHROOM3 | Zornitza Stark Gene: shroom3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2594 | SHROOM3 | Zornitza Stark Phenotypes for gene: SHROOM3 were changed from NEURAL TUBE DEFECT to Anencephaly; cleft lip and palate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2593 | SHROOM3 | Zornitza Stark Classified gene: SHROOM3 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2593 | SHROOM3 | Zornitza Stark Gene: shroom3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2592 | SHROOM3 | Zornitza Stark Mode of inheritance for gene: SHROOM3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2591 | SHROOM3 | Zornitza Stark Publications for gene: SHROOM3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2539 | TRPM7 |
Zornitza Stark changed review comment from: 4 variants identified in a stillbirth cohort. Some supportive evidence that these variants alter channel function.; to: 4 variants identified in a stillbirth cohort. Ion channel expressed in the nervous and cardiac systems. The variant associated with ALS/dementia in the Guam population, p.Thr1482Ile is present in >23,000 hets in gnomad, which is out of keeping for a rare Mendelian disorder. Note recent publication associating missense variants with cardiac arrhythmia and stillbirth, with some functional data provided to substantiate effect of variant on protein function but not necessarily establish gene-disease association. |
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| Fetal anomalies v0.2517 | WNT7A | Seb Lunke Phenotypes for gene: WNT7A were changed from FUHRMANN SYNDROME; LIMB/PELVIS-HYPOPLASIA/APLASIA SYNDROME to Fuhrmann syndrome, MIM# 228930; Ulna and fibula, absence of, with severe limb deficiency, MIM# 276820 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2465 | WDR73 | Zornitza Stark Phenotypes for gene: WDR73 were changed from Galloway-Mowat syndrome 1, 251300; GALLOWAY-MOWAT SYNDROME: MICROCEPHALY AND STEROID-RESISTANT NEPHROTIC SYNDROME to Galloway-Mowat syndrome 1, MIM#251300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2392 | TRAF3IP1 |
Zornitza Stark changed review comment from: 5 unrelated families, zebrafish and mouse models.; to: 5 unrelated families, zebrafish and mouse models. Nephronophthisis is a key feature, polydactyly reported in some. |
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| Fetal anomalies v0.2364 | TECPR2 |
Zornitza Stark changed review comment from: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent. Included due to mild CC abnormalities.; to: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent. Included due to mild CC abnormalities, though clinical presentation is predominantly post-natal. |
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| Fetal anomalies v0.2364 | TECPR2 |
Zornitza Stark changed review comment from: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent; to: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent. Included due to mild CC abnormalities. |
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| Fetal anomalies v0.2352 | MYOD1 | Ain Roesley reviewed gene: MYOD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26733463, 30403323, 31260566; Phenotypes: Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies MIM#618975; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2343 | MECOM | Ain Roesley reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29146883, 29519864, 26581901; Phenotypes: Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 MIM#616738; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2253 | HRAS | Zornitza Stark Marked gene: HRAS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2253 | HRAS | Zornitza Stark Gene: hras has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2253 | HRAS | Zornitza Stark Phenotypes for gene: HRAS were changed from CONGENITAL MYOPATHY WITH EXCESS OF MUSCLE SPINDLES; COSTELLO SYNDROME to Costello syndrome, MIM# 218040 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2252 | HRAS | Zornitza Stark Publications for gene: HRAS were set to 28425981 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2251 | HRAS | Zornitza Stark Mode of pathogenicity for gene: HRAS 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2250 | HRAS | Zornitza Stark Mode of inheritance for gene: HRAS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2249 | HRAS | Zornitza Stark changed review comment from: Well established gene-disease association, over 100 affected individuals reported with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. Facial warts, particularly nasolabial, are often present in childhood.; to: Well established gene-disease association, over 100 affected individuals reported with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2242 | HDAC8 | Zornitza Stark changed review comment from: In a recent series of 246 individuals from diverse populations, congenital diaphragmatic hernia was not a common feature of HDAC8-related CdL.; to: Multiple congenital anomalies are a feature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2239 | HCCS | Zornitza Stark changed review comment from: Diaphragmatic hernia is a recognised feature.; to: Multiple congenital anomalies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2235 | SHROOM3 | Chirag Patel reviewed gene: SHROOM3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32621286; Phenotypes: Anencephaly, cleft lip and palate; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2215 | SMS | Chirag Patel changed review comment from: Snyder-Robinson X-linked syndromic intellectual developmental disorder (MRXSSR) is an X-linked intellectual disability syndrome with characteristic features including facial asymmetry, marfanoid habitus, unsteady gait, thickened lower lip, nasal dysarthric speech, narrow or cleft palate, diminished muscle mass, osteoporosis, kyphoscoliosis, long great toes, short stature, pectus carinatum, and myopia. Does not present antenatally/perinatally. Not suitable for fetal anomalies panel.; to: X-linked syndromic intellectual developmental disorder with characteristic features including dysmorphism, marfanoid habitus, unsteady gait, nasal dysarthric speech, diminished muscle mass, osteoporosis, kyphoscoliosis, long great toes, short stature, pectus carinatum, and myopia. Does not present antenatally. Not suitable for fetal anomalies panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2168 | Zornitza Stark removed gene:TSHR from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2063 | LGI4 | Zornitza Stark Phenotypes for gene: LGI4 were changed from ARTHROGRYPOSIS MULTIPLEX CONGENITA to Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2048 | L1CAM | Zornitza Stark changed review comment from: L1CAM conditions are typically associated with adducted thumb/lower limb spasticity. Single report identified of arthrogryposis.; to: Well established gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1994 | KANSL1 | Zornitza Stark Phenotypes for gene: KANSL1 were changed from CHROMOSOME 17Q21.31 MICRODELETION SYNDROME to Koolen-De Vries syndrome (MIM#610443) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1970 | SMAD4 | Seb Lunke Phenotypes for gene: SMAD4 were changed from JUVENILE POLYPOSIS SYNDROME; MYHRE SYNDROME; JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME to Myhre syndrome, OMIM#139210, MONDO:0007688 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1969 | SMAD4 | Seb Lunke reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myhre syndrome, OMIM#139210, MONDO:0007688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1930 | PI4KA |
Zornitza Stark gene: PI4KA was added gene: PI4KA was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: PI4KA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PI4KA were set to 34415310 Phenotypes for gene: PI4KA were set to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MIM#616531; Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MONDO:0014679 Review for gene: PI4KA was set to GREEN Added comment: 8 families reported with CNS abnormalities. Sources: Expert Review |
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| Fetal anomalies v0.1918 | GLE1 | Zornitza Stark Phenotypes for gene: GLE1 were changed from ARTHROGRYPOSIS, LETHAL, WITH ANTERIOR HORN CELL DISEASE to Lethal congenital contracture syndrome 1, MIM# 253310 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1916 | GLDN | Zornitza Stark Phenotypes for gene: GLDN were changed from Lethal arthroogryposis to Lethal congenital contracture syndrome 11, MIM# 617194; MONDO:0014965 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1875 | TWIST1 | Zornitza Stark Phenotypes for gene: TWIST1 were changed from Craniosynostosis 1, MIM# 123100; Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400; Sweeny-Cox syndrome, MIM# 617746 to Craniosynostosis 1, MIM# 123100; Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400; Sweeny-Cox syndrome, MIM# 617746; Robinow-Sorauf syndrome, MIM# 180750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1874 | SLC25A24 | Seb Lunke Phenotypes for gene: SLC25A24 were changed from Gorlin-Chaudhry-Moss syndrome (GCMS); Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction to Fontaine progeroid syndrome, MIM#612289 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1873 | TWIST1 | Zornitza Stark Phenotypes for gene: TWIST1 were changed from SAETHRE-CHOTZEN SYNDROME; CRANIOSYNOSTOSIS, TYPE 1 to Craniosynostosis 1, MIM# 123100; Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400; Sweeny-Cox syndrome, MIM# 617746 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1871 | UROS | Zornitza Stark Phenotypes for gene: UROS were changed from CONGENITAL ERYTHROPOIETIC PORPHYRIA to Porphyria, congenital erythropoietic, MIM# 263700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1868 | TRPV6 | Alison Yeung reviewed gene: TRPV6: Rating: GREEN; Mode of pathogenicity: None; Publications: 32383311, 31930989, 29861107; Phenotypes: Hyperparathyroidism, transient neonatal, MIM# 618188, Early onset chronic pancreatitis susceptibility; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1866 | TWIST1 | Alison Yeung reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17343269, 9585583, 12116251, 31299755, 30040876; Phenotypes: Craniosynostosis 1, MIM# 123100, Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400, Sweeny-Cox syndrome, MIM# 617746; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1865 | UROS | Alison Yeung reviewed gene: UROS: Rating: RED; Mode of pathogenicity: None; Publications: 24027798, 12533808; Phenotypes: PORPHYRIA, CONGENITAL ERYTHROPOIETIC (MIM #263700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1856 | DSG1 | Zornitza Stark Phenotypes for gene: DSG1 were changed from SEVERE DERMATITIS, MULTIPLE ALLERGIES AND METABOLIC WASTING to Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, AR (MIM#615508) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1854 | DSG1 | Zornitza Stark reviewed gene: DSG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26288349; Phenotypes: Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, AR (MIM#615508); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1844 | DSG1 | Belinda Chong reviewed gene: DSG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19558595, 29315490, 31192455, 23974871, 29229434, 33666035; Phenotypes: Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, AR (MIM#615508), Keratosis palmoplantaris striata I, AD (MIM# 148700); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1837 | GBE1 | Zornitza Stark edited their review of gene: GBE1: Added comment: Three unrelated families reported with severe prenatal presentation of this muscle disorder causing fetal akinesia.; Changed rating: GREEN; Changed publications: 30303820; Changed phenotypes: Glycogen storage disease IV, MIM#232500, Fetal akinesia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1833 | GATA6 | Zornitza Stark Phenotypes for gene: GATA6 were changed from ATRIOVENTRICULAR SEPTAL DEFECT 5; PANCREATIC AGENESIS, DIAPHRAGMATIC HERNIA AND CONGENITAL HEART DEFECTS; ATRIAL SEPTAL DEFECT 9 to Pancreatic agenesis and congenital heart defects, MIM# 600001 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1813 | FREM1 |
Zornitza Stark edited their review of gene: FREM1: Added comment: Bi-allelic variants are associated with multiple congenital anomaly syndromes (MOTA and BNAR), which likely represent a spectrum. Three families reported with trigonocephaly and single missense variants.; Changed rating: GREEN; Changed publications: 32016392, 21931569, 21507892, 19732862, 20301721, 28111185; Changed phenotypes: Manitoba oculotrichoanal syndrome 248450, Bifid nose with or without anorectal and renal anomalies, MIM# 608980, Trigonocephaly 2, MIM# 614485 |
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| Fetal anomalies v0.1812 | SGPL1 | Seb Lunke Phenotypes for gene: SGPL1 were changed from Nephrotic syndrome type 14, 617575; Fetal hydrops to Sphingosine Phosphate Lyase Insufficiency Syndrome; Nephrotic syndrome, type 14, MIM#617575 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1808 | SGPL1 | Seb Lunke reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33074640; Phenotypes: Sphingosine Phosphate Lyase Insufficiency Syndrome, Nephrotic syndrome, type 14, MIM#617575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1704 | Zornitza Stark removed gene:CHRNA4 from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1700 | Zornitza Stark removed gene:CHRNB2 from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1692 | CHRNA4 | Zornitza Stark Marked gene: CHRNA4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1692 | CHRNA4 | Zornitza Stark Gene: chrna4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1692 | CHRNA4 | Zornitza Stark Phenotypes for gene: CHRNA4 were changed from NOCTURNAL FRONTAL LOBE EPILEPSY TYPE 1 to Epilepsy, nocturnal frontal lobe, 1, MIM# 600513 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1691 | CHRNA4 | Zornitza Stark Publications for gene: CHRNA4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1690 | CHRNA4 | Zornitza Stark Mode of inheritance for gene: CHRNA4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1689 | CHRDL1 | Zornitza Stark Marked gene: CHRDL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1689 | CHRDL1 | Zornitza Stark Gene: chrdl1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1689 | CHRDL1 | Zornitza Stark Phenotypes for gene: CHRDL1 were changed from MEGALOCORNEA, X-LINKED to Megalocornea 1, X-linked, MIM# 309300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1688 | CHRDL1 | Zornitza Stark reviewed gene: CHRDL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalocornea 1, X-linked, MIM# 309300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1682 | CCDC65 |
Zornitza Stark changed review comment from: Same homozygous PTC (p.I293Pfs*2) reported in 3 Ashkenzi Jewish families. PMID: 24094744 performs functional assay on null zebrafish model - replicates human phenotype supporting LOF. Three different LoF reported in context of primary ciliary dyskinesia by diagnostic laboratories in ClinVar.; to: Same homozygous PTC (p.I293Pfs*2) reported in 3 Ashkenzi Jewish families. PMID: 24094744 performs functional assay on null zebrafish model - replicates human phenotype supporting LOF. Three different LoF reported in context of primary ciliary dyskinesia by diagnostic laboratories in ClinVar. Situs inversus not reported. |
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| Fetal anomalies v0.1669 | SCO2 | Zornitza Stark Phenotypes for gene: SCO2 were changed from Mitochondrial complex IV deficiency, nuclear type 2, MIM#604377; FATAL INFANTILE CARDIOENCEPHALOMYOPATHY DUE TO CYTOCHROME C OXIDASE DEFICIENCY to Mitochondrial complex IV deficiency, nuclear type 2, MIM# 604377 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1661 | SCO2 | Seb Lunke Phenotypes for gene: SCO2 were changed from FATAL INFANTILE CARDIOENCEPHALOMYOPATHY DUE TO CYTOCHROME C OXIDASE DEFICIENCY to Mitochondrial complex IV deficiency, nuclear type 2, MIM#604377; FATAL INFANTILE CARDIOENCEPHALOMYOPATHY DUE TO CYTOCHROME C OXIDASE DEFICIENCY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1623 | APOPT1 |
Zornitza Stark changed review comment from: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time. Clinical presentation is typically in childhood.; to: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time. Clinical presentation is typically in early childhood. |
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| Fetal anomalies v0.1623 | APOPT1 |
Zornitza Stark changed review comment from: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time.; to: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time. Clinical presentation is typically in childhood. |
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| Fetal anomalies v0.1594 | FGFR2 | Zornitza Stark Phenotypes for gene: FGFR2 were changed from JACKSON-WEISS SYNDROME; FAMILIAL SCAPHOCEPHALY SYNDROME; CROUZON SYNDROME; LACRIMO-AURICULO-DENTO-DIGITAL SYNDROME; BEARE-STEVENSON CUTIS GYRATA SYNDROME; ACROCEPHALOSYNDACTYLY TYPE V; APERT SYNDROME; ANTLEY-BIXLER SYNDROME to LADD syndrome, MIM#149730; Apert syndrome, MIM# 101200; Crouzon syndrome, MIM# 123500; Jackson-Weiss syndrome, MIM# 123150; Pfeiffer syndrome, MIM# 101600; Saethre-Chotzen syndrome, MIM# 101400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1592 | FGFR2 | Zornitza Stark edited their review of gene: FGFR2: Changed phenotypes: LADD syndrome, MIM#149730, Apert syndrome, MIM# 101200, Crouzon syndrome, MIM# 123500, Jackson-Weiss syndrome, MIM# 123150, Pfeiffer syndrome, MIM# 101600, Saethre-Chotzen syndrome, MIM# 101400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1469 | SPRED2 |
Krithika Murali gene: SPRED2 was added gene: SPRED2 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPRED2 were set to 34626534 Phenotypes for gene: SPRED2 were set to cardiac defects; skeletal anomalies Review for gene: SPRED2 was set to GREEN Added comment: Homozygous variants identified in four subjects from three families with a clinical phenotype that included developmental delay, ID, cardiac defects, short stature, skeletal anomalies and dysmorphic features. Cardiac defects and skeletal anomalies potentially ascertainable antenatally. Sources: Expert list, Literature |
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| Fetal anomalies v0.1469 | MESP1 |
Krithika Murali gene: MESP1 was added gene: MESP1 was added to Fetal anomalies. Sources: Literature,Expert list Mode of inheritance for gene: MESP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MESP1 were set to 28677747; 28050627; 27185833; 26694203 Phenotypes for gene: MESP1 were set to Congenital heart disease Review for gene: MESP1 was set to AMBER Added comment: Gene last reviewed April 2021 - Rare/novel variants reported in at least 7 unrelated individuals with congenital heart disease, in-silicos conflicting, familial segregation only available for some (one de novo, three inherited, others unresolved). Functional data implicates gene in cardiac development. No additional published evidence. Sources: Literature, Expert list |
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| Fetal anomalies v0.1469 | FBRSL1 |
Krithika Murali gene: FBRSL1 was added gene: FBRSL1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FBRSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBRSL1 were set to 32424618; 34805182 Phenotypes for gene: FBRSL1 were set to Congenital malformations; congenital heart defect Review for gene: FBRSL1 was set to GREEN Added comment: Associated with novel malformation and intellectual disability syndrome. Three unrelated children with de novo PTCs that escape NMD, with respiratory insufficiency, postnatal growth restriction, microcephaly, global developmental delay and other malformations - 2/3 had heart defects (ASD, VSD), cleft palate and hearing impairement. Supported by Xenopus oocyte functional studies Sources: Literature |
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| Fetal anomalies v0.1441 | DCDC2 | Zornitza Stark Phenotypes for gene: DCDC2 were changed from RENAL-HEPATIC CILIOPATHY to Nephronophthisis 19, MIM# 616217 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1423 | CTNND1 |
Zornitza Stark changed review comment from: 4 individuals from 3 unrelated families with blepharocheilodontic syndrome and mutations in the CTNND1 gene reported originally in PMID 28301459. All had eyelid anomalies, including ectropion of the lower lids, euryblepharon, lagophthalmia, and distichiasis. In addition, all 4 showed typical facial dysmorphism with hypertelorism, flat face, and high forehead, and all had conical teeth and tooth agenesis. Three had cleft lip and palate, 3 had hair anomalies, and 1 had hypothyroidism due to hypoplasia or aplasia of the thyroid gland. None of the patients exhibited anal atresia or neural tube defects. PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. 8/13 patients showed cleft palate. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13). This more recent publication suggests a broader phenotype associated with CTNND1 variants including dev delay, ADHD/ASD, behavioural issues. Unclear from description whether significant ID present. Sources: Literature; to: 4 individuals from 3 unrelated families with blepharocheilodontic syndrome and mutations in the CTNND1 gene reported originally in PMID 28301459. All had eyelid anomalies, including ectropion of the lower lids, euryblepharon, lagophthalmia, and distichiasis. In addition, all 4 showed typical facial dysmorphism with hypertelorism, flat face, and high forehead, and all had conical teeth and tooth agenesis. Three had cleft lip and palate, 3 had hair anomalies, and 1 had hypothyroidism due to hypoplasia or aplasia of the thyroid gland. None of the patients exhibited anal atresia or neural tube defects. PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. 8/13 patients showed cleft palate. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13). This more recent publication suggests a broader phenotype associated with CTNND1 variants including dev delay, ADHD/ASD, behavioural issues. Sources: Literature |
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| Fetal anomalies v0.1423 | CHRNE | Zornitza Stark Marked gene: CHRNE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1423 | CHRNE | Zornitza Stark Gene: chrne has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1423 | CHRNE | Zornitza Stark Classified gene: CHRNE as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1423 | CHRNE | Zornitza Stark Gene: chrne has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1422 | CHRNE | Zornitza Stark changed review comment from: Well established association with congenital myasthenia, some individuals reported with arthrogryposis but cannot find specific reports of multiple pterygium syndrome.; to: Well established association with congenital myasthenia, some individuals reported with arthrogryposis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1422 | CHRNE | Zornitza Stark edited their review of gene: CHRNE: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1361 | ALDH1A2 |
Krithika Murali gene: ALDH1A2 was added gene: ALDH1A2 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ALDH1A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALDH1A2 were set to 33565183; 19886994; 10192400 Phenotypes for gene: ALDH1A2 were set to Congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; thymus aplasia Review for gene: ALDH1A2 was set to GREEN Added comment: Biallellic variants in two unrelated, non-consanguineous families associated with multiple anomalies - including congenital heart disease, eventration of the diaphragm/diaphragmatic hernia, pulmonary hypoplasia dysmorphic features, thymus aplasia - a number of which were detected antenatally. Functional assays suggest the variants in the 2 families are hypomorphic. Knockout mouse model is embryonic lethal due to in utero defects in early heart morphogenesis. Sources: Expert list, Literature |
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| Fetal anomalies v0.1350 | CLTC |
Zornitza Stark changed review comment from: More than 10 unrelated individuals with de novo variants in this gene reported. Individuals with refractory epilepsy were found to carry variants in the first section of the clathrin light chain-binding domain, whereas truncating mutations affecting the C terminus tended to be associated with hypotonia, global developmental delay, and intellectual disability. Hydrocephalus in one individual.; to: More than 10 unrelated individuals with de novo variants in this gene reported. Individuals with refractory epilepsy were found to carry variants in the first section of the clathrin light chain-binding domain, whereas truncating mutations affecting the C terminus tended to be associated with hypotonia, global developmental delay, and intellectual disability. Hydrocephalus in one individual. Microcephaly is acquired. |
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| Fetal anomalies v0.1350 | CLTC |
Zornitza Stark changed review comment from: More than 10 unrelated individuals with de novo variants in this gene reported. Individuals with refractory epilepsy were found to carry variants in the first section of the clathrin light chain-binding domain, whereas truncating mutations affecting the C terminus tended to be associated with hypotonia, global developmental delay, and intellectual disability.; to: More than 10 unrelated individuals with de novo variants in this gene reported. Individuals with refractory epilepsy were found to carry variants in the first section of the clathrin light chain-binding domain, whereas truncating mutations affecting the C terminus tended to be associated with hypotonia, global developmental delay, and intellectual disability. Hydrocephalus in one individual. |
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| Fetal anomalies v0.1259 | NPHS1 | Zornitza Stark Phenotypes for gene: NPHS1 were changed from NEPHROTIC SYNDROME TYPE 1 to Nephrotic syndrome, type 1 (MIM#256300) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1240 | NPHS1 | Daniel Flanagan reviewed gene: NPHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10577936, 17413422; Phenotypes: Nephrotic syndrome, type 1 (MIM#256300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1232 | EFNB1 | Zornitza Stark Phenotypes for gene: EFNB1 were changed from CRANIOFRONTONASAL SYNDROME to Craniofrontonasal dysplasia, MIM# 304110; Diaphragmatic hernia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1230 | CHRNB2 | Zornitza Stark Marked gene: CHRNB2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1230 | CHRNB2 | Zornitza Stark Gene: chrnb2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1230 | CHRNB2 | Zornitza Stark Phenotypes for gene: CHRNB2 were changed from CHRNB2-RELATED NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT; NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT to Epilepsy, nocturnal frontal lobe, 3, MIM# 605375 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1229 | CHRNB2 | Zornitza Stark Publications for gene: CHRNB2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1228 | CHRNB2 | Zornitza Stark Mode of inheritance for gene: CHRNB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1227 | CHRNB2 | Zornitza Stark Classified gene: CHRNB2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1227 | CHRNB2 | Zornitza Stark Gene: chrnb2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1226 | CHRNB2 | Zornitza Stark reviewed gene: CHRNB2: Rating: RED; Mode of pathogenicity: None; Publications: 11062464, 11104662, 19153075, 32536355, 25770198, 23032131; Phenotypes: Epilepsy, nocturnal frontal lobe, 3 605375; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1226 | CHRNB1 | Zornitza Stark Marked gene: CHRNB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1226 | CHRNB1 | Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1226 | CHRNB1 | Zornitza Stark Phenotypes for gene: CHRNB1 were changed from ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314; Myasthenic syndrome, congenital, 2A, slow-channel, 616313 to Myasthenic syndrome, slow-channel congenital, 601462 Myasthenic syndrome, congenital, 2A, slow-channel, 616313; Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1225 | CHRNB1 | Zornitza Stark Publications for gene: CHRNB1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1224 | CHRNB1 | Zornitza Stark Classified gene: CHRNB1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1224 | CHRNB1 | Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1223 | CHRNB1 | Zornitza Stark reviewed gene: CHRNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8872460, 8651643, 27375219, 32504635, 10562302; Phenotypes: Myasthenic syndrome, slow-channel congenital, 601462 Myasthenic syndrome, congenital, 2A, slow-channel, 616313, Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1223 | CHRNA3 | Zornitza Stark Marked gene: CHRNA3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1223 | CHRNA3 | Zornitza Stark Gene: chrna3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1223 | CHRNA3 | Zornitza Stark Phenotypes for gene: CHRNA3 were changed from Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, 191800 to Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, MIM# 191800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1222 | CHRNA3 | Zornitza Stark Publications for gene: CHRNA3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1221 | CHRNA3 | Zornitza Stark Classified gene: CHRNA3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1221 | CHRNA3 | Zornitza Stark Gene: chrna3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1220 | CHRNA3 |
Zornitza Stark changed review comment from: Five individuals from three unrelated families.; to: Five individuals from three unrelated families. Onset is in utero or early childhood. Affected individuals have impaired neuronal bladder and ureteral innervation causing coordination defects that result in secondary structural defects of the renal system, including hydronephrosis, vesicoureteral reflux (VUR), and small kidneys, that may result in chronic kidney disease as well as recurrent urinary tract infections (UTIs). Surgical treatment of VUR is not effective. Most individuals also have additional autonomic features, most commonly impaired pupillary reflex and sometimes orthostatic hypotension. |
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| Fetal anomalies v0.1220 | CHRNA3 | Zornitza Stark reviewed gene: CHRNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31708116; Phenotypes: Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, MIM# 191800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1183 | CD151 | Zornitza Stark Phenotypes for gene: CD151 were changed from NEPHROPATHY WITH PRETIBIAL EPIDERMOLYSIS BULLOSA AND DEAFNESS to Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1180 | CD151 | Zornitza Stark reviewed gene: CD151: Rating: RED; Mode of pathogenicity: None; Publications: 15265795, 29138120; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1176 | CCDC8 | Zornitza Stark changed review comment from: Intellect typically normal; to: 5 unrelated individuals described with the condition; two different homozygous variants described in three individuals. IUGR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1162 | CARS2 |
Zornitza Stark changed review comment from: Three unrelated individuals described with this mitochondrial disorder, ID is part of the phenotype. Sources: Expert list; to: Three unrelated individuals described with this mitochondrial disorder, primarily neurological involvement, post-natal onset. Sources: Expert list |
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| Fetal anomalies v0.1097 | ECEL1 | Zornitza Stark Phenotypes for gene: ECEL1 were changed from DISTAL ARTHROGRYPOSIS TYPE 5D to Arthrogryposis, distal, type 5D, MIM# 615065 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.982 | SCNN1G |
Krithika Murali gene: SCNN1G was added gene: SCNN1G was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SCNN1G was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCNN1G were set to 8640238; 11231969; 31522814; 7633160 Phenotypes for gene: SCNN1G were set to Pseudohypoaldosteronism, type I - MIM#264350 Review for gene: SCNN1G was set to AMBER Added comment: PMID 8640238 - same 3′ splice site mutation in SCNN1G identified in 3 unrelated families from the Indian subcontinent presenting with severe generalised PHA ?founder mutation PMID 11231969 - compound het in Japanese child diagnosed as neonate PMID 31522814 - homozygous variant identified in neonate presenting with nephropathy PMID 7633160 (1995) - PHA reported as likely cause of severe polyhydramnios in 5 patients from 3 unrelated families - not genotyped. SCNN1G related PHA rare diagnosis, possible to present as severe polyhydramnios. Early diagnosis beneficial as PHA can be a life-threatening condition in the neonatal period with therapeutic options available. Sources: Literature |
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| Fetal anomalies v0.982 | MYH9 | Zornitza Stark Phenotypes for gene: MYH9 were changed from MAY-HEGGLIN ANOMALY; FECHTNER SYNDROME; EPSTEIN SYNDROME; MACROTHROMBOCYTOPENIA WITH PROGRESSIVE SENSORINEURAL DEAFNESS; SEBASTIAN SYNDROME; DEAFNESS AUTOSOMAL DOMINANT TYPE 17 to Deafness, autosomal dominant 17 (MIM#603622); Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (MIM#155100) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.957 | DNAH1 |
Krithika Murali gene: DNAH1 was added gene: DNAH1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DNAH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH1 were set to 25927852; 31507630 Phenotypes for gene: DNAH1 were set to Situs inversus; primary ciliary dyskinesia; infertility Review for gene: DNAH1 was set to AMBER Added comment: PMID - 25927852 x2 siblings from consanguineous Saudi family with homozygous missense variants (p.Lys1154Gln). More detailed clinical information available for proband diagnosed with Kartagener syndrome - chronic respiratory infections, situs inversus and infertility. Sister also reported to have been diagnosed with Kartagener syndrome at a similar age but no additional clinical information provided. PMID: 31765523 - 1 patient with PCD with a single het missense. PMID: 24360805 - 7 patients (4 different variants) with homozygous variants and infertility due to defective sperm. Microscopy of sperm revealed dynein disorganization PMID: 31507630 - 1 chet patient with kartagener syndrome, a subtype of PCD. Variants were classified as VUS initially - now c.442C>T (p.Arg148Cys) remains VUS, c.3103C > T p.R1035C re-classified as likely benign. Additional patient was het for a single nonsense, authors acknowledge missed 2nd hit and that this alone was not causative. Currently listed as red gene in Heterotaxy panel Sources: Literature |
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| Fetal anomalies v0.957 | CFAP74 |
Krithika Murali gene: CFAP74 was added gene: CFAP74 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP74 were set to 32555313 Phenotypes for gene: CFAP74 were set to infertility; primary ciliary dyskinesia Review for gene: CFAP74 was set to RED Added comment: Compound het missense variants identified in 2 unrelated patients presenting with male infertility, chronic bronchiectasis and frequent sinusitis. Sources: Literature |
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| Fetal anomalies v0.944 | MYH9 | Daniel Flanagan reviewed gene: MYH9: Rating: AMBER; Mode of pathogenicity: None; Publications: 9390828, 24890873, 17146397, 25505834, 16630581, 16162639, 23976996, 21908426; 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.941 | ANKS6 | Zornitza Stark Phenotypes for gene: ANKS6 were changed from Nephronophthisis 16, 615382 to Nephronophthisis 16, MIM# 615382; MONDO:0014158 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.939 | ANKRD26 | Zornitza Stark Phenotypes for gene: ANKRD26 were changed from THROMBOCYTOPENIA 2 to Thrombocytopaenia 2, MIM# 188000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.935 | ANKRD26 | Zornitza Stark reviewed gene: ANKRD26: Rating: RED; Mode of pathogenicity: None; Publications: 21211618; Phenotypes: Thrombocytopaenia 2, MIM# 188000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.915 | PRRX1 |
Zornitza Stark gene: PRRX1 was added gene: PRRX1 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: PRRX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRRX1 were set to 21294718; 22211708; 22674740; 23444262 Phenotypes for gene: PRRX1 were set to Agnathia-otocephaly complex, MIM# 202650 Review for gene: PRRX1 was set to GREEN Added comment: Agnathia-otocephaly is a rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. The disorder is almost always lethal. Three unrelated individuals reported with heterozygous LoF variants, one family with bi-allelic variants. Sources: Expert Review |
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| Fetal anomalies v0.914 | SLC6A9 | Zornitza Stark Phenotypes for gene: SLC6A9 were changed from Glycine Encephalopathy with Arthrogryposis to Glycine encephalopathy with normal serum glycine 617301; Arthrogryposis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.911 | SLC6A9 | Zornitza Stark commented on gene: SLC6A9: Dempsey et al 2020 (PMID: 31875334) report a fetus with persistently raised NT, hyperextended legs, unilateral talipes. Flexed arms. Small stomach. Consanguineous family. Other reports of SLC6A9 causing arthrogryposis multiplex congenita (presenting prenatally) include: Kurolap et al 2016, PMID: 27773429 (2 families); Hauf et al 2020, PMID: 32712301 (1 family); Mademont-Soler et al 2021, PMID: 33269555 (1 family) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.911 | SLC6A9 | Zornitza Stark edited their review of gene: SLC6A9: Changed publications: 27773429, 27481395, 31875334, 32712301, 33269555; Changed phenotypes: Glycine encephalopathy with normal serum glycine 617301, Arthrogryposis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.903 | ZFPM2 | Zornitza Stark Phenotypes for gene: ZFPM2 were changed from 46XY sex reversal 9 - MIM# 616067; Diaphragmatic hernia 3 - MIM#610187; Tetralogy of Fallot - MIM# 187500 to Diaphragmatic hernia 3 - MIM#610187; Tetralogy of Fallot - MIM# 187500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.902 | ZFPM2 | Zornitza Stark reviewed gene: ZFPM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 3 - MIM#610187, Tetralogy of Fallot - MIM# 187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.886 | ZFPM2 |
Krithika Murali gene: ZFPM2 was added gene: ZFPM2 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ZFPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZFPM2 were set to 16103912; 17568391; 24702427; 10892744; 21919901; 14517948 Phenotypes for gene: ZFPM2 were set to 46XY sex reversal 9 - MIM# 616067; Diaphragmatic hernia 3 - MIM#610187; Tetralogy of Fallot - MIM# 187500 Review for gene: ZFPM2 was set to GREEN Added comment: Associated with congenital diaphragmatic hernia, congenital heart disease and sex reversal. Sources: Expert list, Literature |
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| Fetal anomalies v0.886 | SLIT3 |
Krithika Murali gene: SLIT3 was added gene: SLIT3 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: SLIT3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLIT3 were set to 33933663 Phenotypes for gene: SLIT3 were set to Congenital diaphragmatic hernia Review for gene: SLIT3 was set to AMBER Added comment: Two affected individuals, single family, supportive mouse model. Sources: Expert list, Literature |
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| Fetal anomalies v0.886 | ISLR2 |
Krithika Murali gene: ISLR2 was added gene: ISLR2 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ISLR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISLR2 were set to 30483960 Phenotypes for gene: ISLR2 were set to Hydrocephalus; arthrogryposis Review for gene: ISLR2 was set to AMBER Added comment: Homozygous truncating variant in a single consanguineous family segregated with severe congenital hydrocephalus, arthrogryposis multiplex congenita and abdominal distension. Mouse model also had hydrocephalus. Sources: Expert list, Literature |
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| Fetal anomalies v0.886 | FOXJ1 |
Krithika Murali gene: FOXJ1 was added gene: FOXJ1 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: FOXJ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXJ1 were set to 31630787 Phenotypes for gene: FOXJ1 were set to Ciliary dyskinesia, primary, 43 - MIM# 618699 Review for gene: FOXJ1 was set to GREEN Added comment: Six unrelated individuals with de novo variants in this gene associated with a motile ciliopathy characterized by hydrocephalus, chronic destructive airway disease, and randomization of left/right body asymmetry Sources: Expert list, Literature |
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| Fetal anomalies v0.867 | DHFR | Zornitza Stark changed review comment from: Three unrelated families reported, neurological disease in some severe, others predominantly haematological presentation.; to: Three unrelated families reported, neurological disease in some severe, others predominantly haematological presentation. Earliest presentation was post-natal with acquired microcephaly. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.842 | AMMECR1 | Zornitza Stark reviewed gene: AMMECR1: Rating: RED; Mode of pathogenicity: None; Publications: 27811305, 28089922, 29193635; Phenotypes: Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, MIM# 300990; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.832 | ALG9 | Zornitza Stark changed review comment from: 11 patients from 7 families reported. DD/ID is part of the phenotype.; to: Bi-allelic variants and CDG: At least 7 unrelated families reported, 11 individuals. Clinical features include failure to thrive, dysmorphic features, seizures, hepatic and/or renal cysts; three patients died in utero from a lethal skeletal dysplasia. The severe end of the spectrum is referred to as Gillessen-Kaesbach-Nishimura syndrome and is characterised by skeletal dysplasia, dysmorphic facial features, and variable visceral abnormalities, including polycystic kidneys, diaphragmatic hernia, lung hypoplasia, and congenital heart defects. It may be lethal in utero or early in life. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.797 | MYH8 | Zornitza Stark Phenotypes for gene: MYH8 were changed from CARNEY COMPLEX VARIANT; DISTAL ARTHROGRYPOSIS TYPE to Trismus-pseudocamptodactyly syndrome (MIM#158300) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.774 | ELOVL4 |
Belinda Chong changed review comment from: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects; to: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects |
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| Fetal anomalies v0.771 | ACSL4 | Zornitza Stark changed review comment from: Comment when marking as ready: At least three unrelated individuals reported.; to: Comment when marking as ready: At least three unrelated individuals reported. Microcephaly reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.764 | ABCD4 |
Zornitza Stark changed review comment from: Described clinical features include feeding difficulties, failure to thrive, hypotonia, seizures, developmental delay, and hematological abnormalities. Normal neurodevelopmental outcomes with treatment reported. At least 6 affected individuals reported.; to: Described clinical features include feeding difficulties, failure to thrive, hypotonia, seizures, developmental delay, and haematological abnormalities. Normal neurodevelopmental outcomes with treatment reported. At least 6 affected individuals reported. Congenital anomalies are very rarely reported, uncertain if they are part of the phenotype. |
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| Fetal anomalies v0.720 | CTC1 |
Zornitza Stark edited their review of gene: CTC1: Added comment: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), also known as Coats plus syndrome, is an autosomal recessive pleomorphic disorder characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline. Patients also have retinal telangiectasia and exudates (Coats disease) as well as extraneurologic manifestations, including osteopenia with poor bone healing and a high risk of gastrointestinal bleeding and portal hypertension caused by vasculature ectasias in the stomach, small intestine, and liver. Some individuals also have hair, skin, and nail changes, as well as anaemia and thrombocytopaenia. Multiple families reported.; Changed rating: GREEN; Changed publications: 22267198 |
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| Fetal anomalies v0.669 | UNC50 | Zornitza Stark Phenotypes for gene: UNC50 were changed from to Arthrogryposis multiplex congenita | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.660 | EN1 |
Krithika Murali gene: EN1 was added gene: EN1 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EN1 were set to 33568816 Phenotypes for gene: EN1 were set to ?ENDOVE syndrome, limb-brain type - OMIM#619218 Review for gene: EN1 was set to GREEN Added comment: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. An additional fourth individual had cerebellar hypoplasia in addition to the skeletal phenotype, and a bi-allelic LoF variant. Sources: Expert list, Literature |
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| Fetal anomalies v0.655 | MMP13 | Zornitza Stark Phenotypes for gene: MMP13 were changed from SPONDYLOEPIMETAPHYSEAL DYSPLASIA MISSOURI TYPE; METAPHYSEAL ANADYSPLASIA TYPE 1 to Metaphyseal anadysplasia 1 (MIM#602111); Metaphyseal dysplasia, Spahr type (MIM#250400) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.650 | SCN5A |
Krithika Murali gene: SCN5A was added gene: SCN5A was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SCN5A were set to 22064211; 15184283; 19419784 Phenotypes for gene: SCN5A were set to Sudden infant death syndrome, susceptibility to - #272120; Long QT syndrome 3 - #603830 Review for gene: SCN5A was set to GREEN Added comment: Three families reported with severe perinatal presentation, including hydrops Sources: Expert list, Literature |
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| Fetal anomalies v0.645 | KLF1 | Zornitza Stark Phenotypes for gene: KLF1 were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV; Hydrops Fetalis to Dyserythropoietic anaemia, congenital, type IV MIM#613673 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.612 | ZBTB42 |
Krithika Murali gene: ZBTB42 was added gene: ZBTB42 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ZBTB42 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZBTB42 were set to 25055871 Phenotypes for gene: ZBTB42 were set to ?Lethal congenital contracture syndrome 6- #616248 Review for gene: ZBTB42 was set to AMBER Added comment: Homozygous missense variant reported in a family with three stillbirths and a phenotype consistent with LCCS. Supportive zebrafish model. Sources: Expert list, Literature |
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| Fetal anomalies v0.612 | UNC50 | Krithika Murali reviewed gene: UNC50: Rating: ; Mode of pathogenicity: None; Publications: 29016857, 33820833; Phenotypes: Arthrogryposis multiplex congenita; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.612 | STIM1 |
Krithika Murali gene: STIM1 was added gene: STIM1 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: STIM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: STIM1 were set to 31448844; 20876309 Phenotypes for gene: STIM1 were set to Immunodeficiency 10 - #612783; Myopathy, tubular aggregate, 1 - #160565; Stormorken syndrome - #185070 Review for gene: STIM1 was set to GREEN Added comment: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence) Dominant STIM1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias) Recessive STIM1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy) --> presentations can be severe, death from disseminated Kaposi sarcoma in an HIV negative 2 year old F reported. Highly variable phenotype - contractures have been reported in the more severely affected individuals. Sources: Expert list, Literature |
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| Fetal anomalies v0.612 | SCYL2 |
Krithika Murali gene: SCYL2 was added gene: SCYL2 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCYL2 were set to 31960134; 26203146 Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum - #618766 Review for gene: SCYL2 was set to AMBER Added comment: 2 unrelated consanguineous families reported with AMC (PMID: 31960134). Constitutive mouse knockout of Scyl2 results in neonatal lethality and severe motor and sensory deficits (PMID: 26203146). Sources: Expert list, Literature |
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| Fetal anomalies v0.612 | ORAI1 |
Krithika Murali gene: ORAI1 was added gene: ORAI1 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ORAI1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ORAI1 were set to 31448844 Phenotypes for gene: ORAI1 were set to Myopathy, tubular aggregate, 2 - #615883 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) Sources: Expert list, Literature |
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| Fetal anomalies v0.612 | MYLPF |
Krithika Murali gene: MYLPF was added gene: MYLPF was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: MYLPF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MYLPF were set to 32707087 Phenotypes for gene: MYLPF were set to Distal arthrogryposis type 1C (DA1C), MIM#619110 Review for gene: MYLPF was set to AMBER Added comment: MYLPF gene variants associated with dominant and recessive distal arthrogryposis 6 consanguineous families - homozygous for c.470G>T (p.Cys157Phe) or c.469T>C (p.Cys157Arg) variants 7th family - hetrozygous c.487G>A (p.Gly163Ser) variant 8th family - hetrozygous c.98C>T (p.Ala33Val) variant Sources: Expert list, Literature |
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| Fetal anomalies v0.587 | MMP13 |
Daniel Flanagan changed review comment from: At least 7 families described with either mono or biallelic variants reports. Autosomal dominant metaphyseal anadysplasia has been described as more severe, with dominant-negative missense mutations in the prodomain of MMP13 that determine autoactivation of MMP13 and intracellular degradation of both MMP13 and MMP9, resulting in a double enzymatic deficiency. Recessive metaphyseal anadysplasia has been described as a milder form, caused by biallelic loss of function of either MMP9 or MMP13.; to: At least 7 families described with either mono (Metaphyseal anadysplasia) or biallelic (Metaphyseal dysplasia, Spahr type) variants reports. Autosomal dominant metaphyseal anadysplasia has been described as more severe, with dominant-negative missense mutations in the prodomain of MMP13 that determine autoactivation of MMP13 and intracellular degradation of both MMP13 and MMP9, resulting in a double enzymatic deficiency. Recessive metaphyseal anadysplasia has been described as a milder form, caused by biallelic loss of function of either MMP9 or MMP13. |
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| Fetal anomalies v0.584 | MMP13 | Daniel Flanagan reviewed gene: MMP13: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19615667, 24781753, 24648384; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400), ?Spondyloepimetaphyseal dysplasia, Missouri type (MIM#602111); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.582 | KLF1 | Ain Roesley reviewed gene: KLF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300242, 25724378, 28265383; Phenotypes: Blood group--Lutheran inhibitor MIM#111150, Dyserythropoietic anemia, congenital, type IV MIM#613673; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.572 | COL1A2 | Zornitza Stark Phenotypes for gene: COL1A2 were changed from Osteogenesis imperfecta; Ehlers-Danlos syndrome to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120; Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821; Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320; Osteogenesis imperfecta, type II, MIM# 166210; Osteogenesis imperfecta, type III, MIM# 259420; Osteogenesis imperfecta, type IV, MIM# 166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.571 | COL1A2 | Zornitza Stark edited their review of gene: COL1A2: Added comment: Well established gene-disease associations, likely representing a spectrum. The more severe phenotypes can present antenatally particularly with skeletal features.; Changed rating: GREEN; Changed phenotypes: Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120, Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821, Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320, Osteogenesis imperfecta, type II, MIM# 166210, Osteogenesis imperfecta, type III, MIM# 259420, Osteogenesis imperfecta, type IV, MIM# 166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.571 | COL1A1 | Zornitza Stark Phenotypes for gene: COL1A1 were changed from OSTEOGENESIS IMPERFECTA TYPE III; CAFFEY DISEASE; OSTEOGENESIS IMPERFECTA TYPE I; OSTEOGENESIS IMPERFECTA TYPE IIA; EHLERS-DANLOS SYNDROME TYPE VIIA; COL1A1/2-RELATED OSTEOGENESIS IMPERFECTA; EHLERS-DANLOS SYNDROME, CLASSIC TYPE, COL1A1-RELATED to Caffey disease, MIM#114000; Ehlers-Danlos syndrome, arthrochalasia type, 1, MIM#130060; Osteogenesis imperfecta, type I, MIM#166200; Osteogenesis imperfecta, type II, MIM#166210; Osteogenesis imperfecta, type III, MIM#259420; Osteogenesis imperfecta, type IV, MIM#166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.558 | COG7 |
Zornitza Stark changed review comment from: CDG IIe is caused by variants that impair the integrity of the conserved oligomeric Golgi (COG) complex and alter Golgi trafficking, resulting in the disruption of multiple glycosylation pathways. Three families reported, IVS1+4A-C variant is recurrent, supportive functional data.; to: CDG IIe is caused by variants that impair the integrity of the conserved oligomeric Golgi (COG) complex and alter Golgi trafficking, resulting in the disruption of multiple glycosylation pathways. Three families reported, IVS1+4A-C variant is recurrent, supportive functional data. IUGR is a feature. |
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| Fetal anomalies v0.553 | COASY | Zornitza Stark Phenotypes for gene: COASY were changed from NEURODEGENERATION WITH BRAIN IRON ACCUMULATION to Pontocerebellar hypoplasia; microcephaly; arthrogryposis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.551 | COASY |
Zornitza Stark changed review comment from: Two families reported with a severe, prenatal onset phenotype comprising PCH, microcephaly and arthrogryposis. Note gene is also associated with NBIA. Sources: Expert list; to: Two families reported with a severe, prenatal onset phenotype comprising PCH, microcephaly and arthrogryposis. Note gene is also associated with NBIA but this presents postnatally. Sources: Expert list |
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| Fetal anomalies v0.539 | ATP1A2 | Zornitza Stark Phenotypes for gene: ATP1A2 were changed from hydrops fetalis; arthrogryposis; microcephaly; extensive cortical malformations to Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602; Developmental and epileptic encephalopathy, polymicrogyria | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.535 | ATP1A2 | Zornitza Stark commented on gene: ATP1A2: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal. This is a distinct phenotype from the mono allelic variants associated with alternating hemiplegia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.505 | CHRNG | Zornitza Stark Marked gene: CHRNG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.505 | CHRNG | Zornitza Stark Gene: chrng has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.505 | CHRNG | Zornitza Stark Phenotypes for gene: CHRNG were changed from MULTIPLE PTERYGIUM SYNDROME ESCOBAR VARIANT to Escobar syndrome, MIM# 265000; Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009926; MONDO:0009668 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.504 | CHRNG | Zornitza Stark Publications for gene: CHRNG were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.503 | CHRND | Zornitza Stark Phenotypes for gene: CHRND were changed from Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009668; Myasthenic syndrome, congenital, 1A, slow-channel, MIM# 601462; Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930 to Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009668 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.502 | CHRND | Zornitza Stark Phenotypes for gene: CHRND were changed from Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009668; Myasthenic syndrome, congenital, 1A, slow-channel, MIM# 601462; Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930 to Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009668; Myasthenic syndrome, congenital, 1A, slow-channel, MIM# 601462; Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.501 | CHRND | Zornitza Stark Marked gene: CHRND as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.501 | CHRND | Zornitza Stark Gene: chrnd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.501 | CHRND | Zornitza Stark Phenotypes for gene: CHRND were changed from Several associated, probably most relevant is lethal multiple pterygium syndrome 253290 to Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009668; Myasthenic syndrome, congenital, 1A, slow-channel, MIM# 601462; Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.500 | CHRND | Zornitza Stark Publications for gene: CHRND were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.499 | CHRNA1 | Zornitza Stark Marked gene: CHRNA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.499 | CHRNA1 | Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.499 | CHRNA1 | Zornitza Stark Phenotypes for gene: CHRNA1 were changed from Multiple pterygium syndrome, lethal type, 253290; MULTIPLE PTERYGIUM SYNDROME LETHAL TYPE to Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009668 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.448 | ITGA6 |
Ain Roesley changed review comment from: At least 4 probands reported Pyelonephrosis, Urethrovesical occlusion and Stenosis at the ureterovesical junctions are some other features in this condition; to: At least 4 probands reported Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; and ureteral and renal anomalies (dysplastic/multicystic kidney, hydronephrosis/hydroureter, ureterocele, duplicated renal collecting system, absent bladder). |
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| Fetal anomalies v0.432 | CEP83 | Zornitza Stark Phenotypes for gene: CEP83 were changed from INFANTILE NEPHRONOPHTHISIS AND INTELLECTUAL DISABILITY to Nephronophthisis 18, MIM# 615862; MONDO:0014374; Hydrocephalus; ID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.423 | CEP164 | Zornitza Stark Phenotypes for gene: CEP164 were changed from Nephronophthisis 15 614845 to Bardet-Biedl syndrome; Nephronophthisis 15, MIM# 614845; Oro-facio-digital syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.417 | CEP120 | Zornitza Stark edited their review of gene: CEP120: Added comment: More than 5 unrelated families with JBTS reported, and at least three families with SRTD. Functional data.; Changed publications: 27208211, 33486889, 29847808, 25361962, 27208211; Changed phenotypes: Joubert syndrome 31, MIM# 617761, Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.417 | CEP104 |
Zornitza Stark changed review comment from: Three unrelated individuals reported, ID is part of the phenotype. Sources: Expert list; to: Three unrelated individuals reported, structural brain abnormalities are part of the phenotype. Sources: Expert list |
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| Fetal anomalies v0.393 | CDAN1 | Zornitza Stark Phenotypes for gene: CDAN1 were changed from Anemia, congenital dyserythropoietic, type 1a, MONDO:0009135; Dyserythropoietic anemia, congenital, type Ia, OMIM:224120 to Dyserythropoietic anemia, congenital, type Ia, OMIM#224120 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.391 | CDAN1 | Zornitza Stark reviewed gene: CDAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32518175; Phenotypes: Dyserythropoietic anemia, congenital, type Ia, 224120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.371 | CASK | Zornitza Stark changed review comment from: FG syndrome is listed in review articles of arthrogryposis-associated conditions, however I am unable to find specific reports of contractures, or mention of contractures in reviews of CASK-related disorders.; to: CASK-related disorders have microcephaly and structural brain abnormalities as features. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.331 | BMPER |
Zornitza Stark changed review comment from: Perinatal lethal skeletal dysplasia. The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases; to: Perinatal lethal skeletal dysplasia. The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases. At least 5 unrelated families reported. |
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| Fetal anomalies v0.331 | BMPER |
Zornitza Stark changed review comment from: Perinatal lethal skeletal dysplasia.; to: Perinatal lethal skeletal dysplasia. The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases |
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| Fetal anomalies v0.273 | DKC1 | Zornitza Stark Phenotypes for gene: DKC1 were changed from DKC1-RELATED DYSKERATOSIS CONGENITA; DYSKERATOSIS CONGENITA, X-LINKED to Dyskeratosis congenita, X-linked MIM#305000; Hoyeraal-Hreidarsson syndrome (HHS) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.247 | HR | Zornitza Stark Marked gene: HR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.247 | HR | Zornitza Stark Gene: hr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.247 | HR | Zornitza Stark Phenotypes for gene: HR were changed from ATRICHIA WITH PAPULAR LESIONS; ALOPECIA UNIVERSALIS to Atrichia with papular lesions MIM#209500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.246 | HR | Zornitza Stark Classified gene: HR as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.246 | HR | Zornitza Stark Gene: hr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.214 | TOP2B |
Zornitza Stark gene: TOP2B was added gene: TOP2B was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TOP2B were set to 31409799 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 GREEN Added comment: Four individuals from three unrelated families reported, all the variants affected the TOPRIM domain, functional data including mouse model. Sources: Expert Review |
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| Fetal anomalies v0.204 | ATAD3A | Zornitza Stark Phenotypes for gene: ATAD3A were changed from ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810; Harel-Yoon syndrome, OMIM:617183 to Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.200 | ASXL1 | Zornitza Stark Phenotypes for gene: ASXL1 were changed from BOHRING-OPITZ SYNDROME to Bohring-Opitz syndrome , MIM#605039 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.197 | ASXL1 | Zornitza Stark changed review comment from: Colobomas reported.; to: Bohring-Opitz syndrome is a malformation syndrome characterized by severe intrauterine growth retardation, poor feeding, profound ID, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints -- many of these features would be identifiable antenatally. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.190 | ASCC1 | Zornitza Stark Phenotypes for gene: ASCC1 were changed from spinal muscular atrophy; hypotonia; contractures; fetal akinesia; arthrogryposis to Spinal muscular atrophy with congenital bone fractures 2 MIM#616867 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.180 | ARSA | Zornitza Stark Phenotypes for gene: ARSA were changed from ARYLSULFATASE A DEFICIENCY to Metachromatic leukodystrophy, MIM# 250100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.177 | ARSA | Zornitza Stark reviewed gene: ARSA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metachromatic leukodystrophy, MIM# 250100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.158 | ATAD1 |
Krithika Murali gene: ATAD1 was added gene: ATAD1 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ATAD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATAD1 were set to 28180185; 29390050; 29659736 Phenotypes for gene: ATAD1 were set to Hyperekplexia 4 - #618011 Review for gene: ATAD1 was set to GREEN Added comment: Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Three unrelated families reported. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures. Severe progressive neurological disorder, severe/profound intellectual disability is a feature. Sources: Expert list, Literature |
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| Fetal anomalies v0.158 | ADCY6 |
Krithika Murali gene: ADCY6 was added gene: ADCY6 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADCY6 were set to 24319099, 26257172, 31846058; 33820833 Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8 - #616287 Review for gene: ADCY6 was set to GREEN Added comment: PMID: 33820833 (2021) - Further 2 sibs reported with a homozygous c.3346C>T:p.Arg1116Cys variant in the ADCY6 gene. The family was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and IUGR were detected prenatally. Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies. Sources: Expert list, Literature |
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| Fetal anomalies v0.152 | HSD17B3 | Ain Roesley reviewed gene: HSD17B3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohermaphroditism, male, with gynecomastia MIM#264300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.152 | HR | Ain Roesley reviewed gene: HR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrichia with papular lesions MIM#209500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.143 | ITGA3 | Zornitza Stark Phenotypes for gene: ITGA3 were changed from INTERSTITIAL LUNG DISEASE, NEPHROTIC SYNDROME, AND EPIDERMOLYSIS BULLOSA, CONGENITAL to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.141 | ITGA3 | Zornitza Stark reviewed gene: ITGA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22512483, 25810266, 27717396, 32198874, 26854491, 23114595, 30466509; Phenotypes: Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.140 | EFEMP2 |
Zornitza Stark gene: EFEMP2 was added gene: EFEMP2 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: EFEMP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EFEMP2 were set to 30140196; 23532871; 31548410; 19664000 Phenotypes for gene: EFEMP2 were set to Autosomal recessive cutis laxa type 1B (ARCL1B), MIM# 614437 Review for gene: EFEMP2 was set to GREEN Added comment: Associated with pulmonary hypoplasia, hypoplastic diaphragm and diffuse lung disease, fractures, arthrogryposis. Over 20 unrelated families reported in the literature. Sources: Expert Review |
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| Fetal anomalies v0.139 | HBA2 | Ain Roesley reviewed gene: HBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thalassemias, alpha- , MIM#604131, Heinz body anemias, alpha-, MIM# 140700, Erythrocytosis 7, MIM# 617981; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.139 | HBA1 | Ain Roesley reviewed gene: HBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thalassemias, alpha- , MIM#604131, Heinz body anemias, alpha-, MIM# 140700, Erythrocytosis 7, MIM# 617981; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.135 | QRICH1 |
Zornitza Stark changed review comment from: Eight unrelated individuals reported with expressive speech delay, moderate motor delay, learning difficulties/ mild ID, mild microcephaly, short stature and notable social behaviour deficits as clinical hallmarks. One individual reported with nephroblastoma.; to: Eight unrelated individuals reported with expressive speech delay, moderate motor delay, learning difficulties/ mild ID, mild microcephaly, short stature and notable social behaviour deficits as clinical hallmarks. One individual reported with nephroblastoma. IUGR rarely reported. Other features are unlikely to be detectable perinatally. |
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| Fetal anomalies v0.132 | BICD2 | Zornitza Stark Phenotypes for gene: BICD2 were changed from reduced fetal movements; PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); hydrops fetalis; Pterygium to Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant 615290; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant 618291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.107 | ALG6 |
Zornitza Stark changed review comment from: Over 100 affected individuals reported. PMID 27498540 summarises findings in 41 patients. Hypotonia and developmental delay were reported in all. Other common features include epilepsy, ataxia, proximal muscle weakness, and, in the majority of cases, failure to thrive. Nine patients developed intractable seizures. Coagulation anomalies were present in <50 % of cases, without spontaneous bleedings. Facial dysmorphism was rare, but seven patients showed missing phalanges and brachydactyly. Cyclic behavioral change, with autistic features and depressive episodes. Eleven children died before the age of 4 years due to protein losing enteropathy (PLE), sepsis, or seizures. The oldest patient was a 40 year-old. The most common pathogenic protein alterations were p.A333V and p.I299Del, without any clear genotype-phenotype correlation.; to: Over 100 affected individuals reported. Mostly neurological features, though rare congenital anomalies such as missing phalanges reported. PMID 27498540 summarises findings in 41 patients. Hypotonia and developmental delay were reported in all. Other common features include epilepsy, ataxia, proximal muscle weakness, and, in the majority of cases, failure to thrive. Nine patients developed intractable seizures. Coagulation anomalies were present in <50 % of cases, without spontaneous bleedings. Facial dysmorphism was rare, but seven patients showed missing phalanges and brachydactyly. Cyclic behavioral change, with autistic features and depressive episodes. Eleven children died before the age of 4 years due to protein losing enteropathy (PLE), sepsis, or seizures. The oldest patient was a 40 year-old. The most common pathogenic protein alterations were p.A333V and p.I299Del, without any clear genotype-phenotype correlation. |
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| Fetal anomalies v0.101 | ADAR | Zornitza Stark Phenotypes for gene: ADAR were changed from AICARDI-GOUTIERES SYNDROME ASSOCIATED WITH A TYPE I INTERFERON SIGNATURE; DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1 to Aicardi-Goutieres syndrome 6, MIM# 615010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.67 | AGTR1 |
Zornitza Stark gene: AGTR1 was added gene: AGTR1 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: AGTR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGTR1 were set to 16116425 Phenotypes for gene: AGTR1 were set to Renal tubular dysgenesis, MIM# 267430 Added comment: Three unrelated families reported. Severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Sources: Expert Review |
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| Fetal anomalies v0.54 | ADGRG6 | Zornitza Stark changed review comment from: Three other families reported but with severe prenatal onset arthrogryposis, unclear if CNS features.; to: Three other families reported but with severe prenatal onset arthrogryposis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.36 | ACTC1 | Zornitza Stark changed review comment from: Well established association with cardiomyopathies. Three families reported with ASD.; to: Well established association with cardiomyopathies. Four families reported with ASD. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | TSHR |
Zornitza Stark gene: TSHR was added gene: TSHR was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: TSHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: TSHR were set to HYPERTHYROIDISM, FAMILIAL GESTATIONAL; HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 1 |
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| Fetal anomalies v0.0 | TSHB |
Zornitza Stark gene: TSHB was added gene: TSHB was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: TSHB was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TSHB were set to HYPOTHRYOIDISM, CONGENITAL, NONGOITROUS 4 |
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| Fetal anomalies v0.0 | TIMM8A |
Zornitza Stark gene: TIMM8A was added gene: TIMM8A was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: TIMM8A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: TIMM8A were set to JENSEN SYNDROME; MOHR-TRANEBJAERG SYNDROME |
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| Fetal anomalies v0.0 | SLC9A6 |
Zornitza Stark gene: SLC9A6 was added gene: SLC9A6 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SLC9A6 were set to MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE |
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| Fetal anomalies v0.0 | SHROOM4 |
Zornitza Stark gene: SHROOM4 was added gene: SHROOM4 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: SHROOM4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SHROOM4 were set to 32565546 Phenotypes for gene: SHROOM4 were set to Stocco dos Santos X-linked mental retardation syndrome, 300434 |
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| Fetal anomalies v0.0 | SCN1A |
Zornitza Stark gene: SCN1A was added gene: SCN1A was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SCN1A were set to 29543227; 32928894 Phenotypes for gene: SCN1A were set to Dravet syndrome, OMIM:607208; Arthrogryposis multiplex congenita |
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| Fetal anomalies v0.0 | PLCE1 |
Zornitza Stark gene: PLCE1 was added gene: PLCE1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: PLCE1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PLCE1 were set to NEPHROTIC SYNDROME, TYPE 3 |
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| Fetal anomalies v0.0 | NPHS2 |
Zornitza Stark gene: NPHS2 was added gene: NPHS2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: NPHS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHS2 were set to NEPHROTIC SYNDROME, TYPE 2 |
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| Fetal anomalies v0.0 | MECP2 |
Zornitza Stark gene: MECP2 was added gene: MECP2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: MECP2 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: MECP2 were set to 30712880 Phenotypes for gene: MECP2 were set to MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 13; MENTAL RETARDATION SYNDROMIC X-LINKED LUBS TYPE; CHROMOSOME XQ28 DUPLICATION SYNDROME; ENCEPHALOPATHY NEONATAL SEVERE DUE TO MECP2 MUTATIONS; RETT SYNDROME (RTT)[ |
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| Fetal anomalies v0.0 | HPGD |
Zornitza Stark gene: HPGD was added gene: HPGD was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: HPGD was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HPGD were set to CRANIOOSTEOARTHROPATHY |
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| Fetal anomalies v0.0 | GJB2 |
Zornitza Stark gene: GJB2 was added gene: GJB2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: GJB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GJB2 were set to 24346921; 23035047 Phenotypes for gene: GJB2 were set to DEAFNESS AUTOSOMAL RECESSIVE TYPE 1A; BART-PUMPHREY SYNDROME; VOHWINKEL SYNDROME; ICHTHYOSIS HYSTRIX-LIKE WITH DEAFNESS SYNDROME; PALMOPLANTAR KERATODERMA WITH DEAFNESS |
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| Fetal anomalies v0.0 | GHR |
Zornitza Stark gene: GHR was added gene: GHR was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: GHR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GHR were set to PITUITARY DWARFISM II |
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| Fetal anomalies v0.0 | CTNS |
Zornitza Stark gene: CTNS was added gene: CTNS was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: CTNS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CTNS were set to CYSTINOSIS NEPHROPATHIC TYPE; CYSTINOSIS LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE; CYSTINOSIS ADULT NON-NEPHROPATHIC TYPE |
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| Fetal anomalies v0.0 | CHRNA4 |
Zornitza Stark gene: CHRNA4 was added gene: CHRNA4 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: CHRNA4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CHRNA4 were set to NOCTURNAL FRONTAL LOBE EPILEPSY TYPE 1 |
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| Fetal anomalies v0.0 | CHRDL1 |
Zornitza Stark gene: CHRDL1 was added gene: CHRDL1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: CHRDL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CHRDL1 were set to MEGALOCORNEA, X-LINKED |
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| Fetal anomalies v0.0 | ZNF423 |
Zornitza Stark gene: ZNF423 was added gene: ZNF423 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: ZNF423 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ZNF423 were set to 22863007 Phenotypes for gene: ZNF423 were set to Joubert syndrome 19 614844; Nephronophthisis 14 614844 |
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| Fetal anomalies v0.0 | WDR73 |
Zornitza Stark gene: WDR73 was added gene: WDR73 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: WDR73 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WDR73 were set to Galloway-Mowat syndrome 1, 251300; GALLOWAY-MOWAT SYNDROME: MICROCEPHALY AND STEROID-RESISTANT NEPHROTIC SYNDROME |
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| Fetal anomalies v0.0 | TOR1A |
Zornitza Stark gene: TOR1A was added gene: TOR1A was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: TOR1A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOR1A were set to 30244176; 28516161; 29053766 Phenotypes for gene: TOR1A were set to Arthrogryposis multiplex congenita 5, OMIM:618947; Arthrogryposis multiplex congenita 5, MONDO:0100218 |
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| Fetal anomalies v0.0 | TNNT3 |
Zornitza Stark gene: TNNT3 was added gene: TNNT3 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: TNNT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TNNT3 were set to 25337069; 32779773; 21402185; 17194691; 19142688 Phenotypes for gene: TNNT3 were set to Arthrogryposis, distal, type 2B2, OMIM:618435; Arthrogryposis, distal, type 2B2, MONDO:0032750 Mode of pathogenicity for gene: TNNT3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments |
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| Fetal anomalies v0.0 | SYNE1 |
Zornitza Stark gene: SYNE1 was added gene: SYNE1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SYNE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SYNE1 were set to 27782104; 19542096; 24319099 Phenotypes for gene: SYNE1 were set to Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484; Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778 |
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| Fetal anomalies v0.0 | SMPD4 |
Zornitza Stark gene: SMPD4 was added gene: SMPD4 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SMPD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMPD4 were set to 31495489 Phenotypes for gene: SMPD4 were set to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, MONDO:0032838; Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, OMIM:618622 |
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| Fetal anomalies v0.0 | SLC6A9 |
Zornitza Stark gene: SLC6A9 was added gene: SLC6A9 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SLC6A9 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC6A9 were set to Glycine Encephalopathy with Arthrogryposis |
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| Fetal anomalies v0.0 | SHROOM3 |
Zornitza Stark gene: SHROOM3 was added gene: SHROOM3 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SHROOM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SHROOM3 were set to NEURAL TUBE DEFECT |
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| Fetal anomalies v0.0 | PDE6H |
Zornitza Stark gene: PDE6H was added gene: PDE6H was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: PDE6H was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PDE6H were set to ACHROMATOPSIA; RETINAL CONE DYSTROPHY 3 PDE6H |
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| Fetal anomalies v0.0 | NEK9 |
Zornitza Stark gene: NEK9 was added gene: NEK9 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: NEK9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEK9 were set to 26908619; 26633546; 32333414; 21271645 Phenotypes for gene: NEK9 were set to Arthrogryposis, Perthes disease, and upward gaze palsy, MONDO:0013660; NEK9-related lethal skeletal dysplasia, MONDO:0014870; Lethal congenital contracture syndrome 10, OMIM:617022; ?Arthrogryposis, Perthes disease, and upward gaze palsy, OMIM:614262 |
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| Fetal anomalies v0.0 | NEK8 |
Zornitza Stark gene: NEK8 was added gene: NEK8 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: NEK8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEK8 were set to 26697755; 18199800; 26967905; 26862157; 23418306 Phenotypes for gene: NEK8 were set to Renal-hepatic-pancreatic dysplasia 2, MONDO:0014174; Renal-hepatic-pancreatic dysplasia 2, OMIM:615415; ?Nephronophthisis 9, OMIM:613824; Nephronophthisis 9, MONDO:0013444 |
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| Fetal anomalies v0.0 | MYOD1 |
Zornitza Stark gene: MYOD1 was added gene: MYOD1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: MYOD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYOD1 were set to 30403323; 26733463; 31260566 Phenotypes for gene: MYOD1 were set to Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, OMIM:618975 |
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| Fetal anomalies v0.0 | MECOM |
Zornitza Stark gene: MECOM was added gene: MECOM was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: MECOM was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MECOM were set to Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia |
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| Fetal anomalies v0.0 | GLIS2 |
Zornitza Stark gene: GLIS2 was added gene: GLIS2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: GLIS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GLIS2 were set to NEPHRONOPHTHISIS 7 |
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| Fetal anomalies v0.0 | CHRNE |
Zornitza Stark gene: CHRNE was added gene: CHRNE was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CHRNE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: CHRNE were set to Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931 |
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| Fetal anomalies v0.0 | CHRNB2 |
Zornitza Stark gene: CHRNB2 was added gene: CHRNB2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CHRNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CHRNB2 were set to CHRNB2-RELATED NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT; NOCTURNAL FRONTAL LOBE EPILEPSY, AUTOSOMAL DOMINANT |
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| Fetal anomalies v0.0 | CHRNB1 |
Zornitza Stark gene: CHRNB1 was added gene: CHRNB1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CHRNB1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: CHRNB1 were set to ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314; Myasthenic syndrome, congenital, 2A, slow-channel, 616313 |
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| Fetal anomalies v0.0 | CHRNA3 |
Zornitza Stark gene: CHRNA3 was added gene: CHRNA3 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHRNA3 were set to Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, 191800 |
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| Fetal anomalies v0.0 | CD151 |
Zornitza Stark gene: CD151 was added gene: CD151 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CD151 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CD151 were set to NEPHROPATHY WITH PRETIBIAL EPIDERMOLYSIS BULLOSA AND DEAFNESS |
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| Fetal anomalies v0.0 | ATP1A2 |
Zornitza Stark gene: ATP1A2 was added gene: ATP1A2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP1A2 were set to 31608932; 30690204 Phenotypes for gene: ATP1A2 were set to hydrops fetalis; arthrogryposis; microcephaly; extensive cortical malformations |
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| Fetal anomalies v0.0 | ANKS6 |
Zornitza Stark gene: ANKS6 was added gene: ANKS6 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: ANKS6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ANKS6 were set to Nephronophthisis 16, 615382 |
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| Fetal anomalies v0.0 | ANKRD26 |
Zornitza Stark gene: ANKRD26 was added gene: ANKRD26 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: ANKRD26 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ANKRD26 were set to THROMBOCYTOPENIA 2 |
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| Fetal anomalies v0.0 | AMMECR1 |
Zornitza Stark gene: AMMECR1 was added gene: AMMECR1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: AMMECR1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AMMECR1 were set to Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, 300990 |
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| Fetal anomalies v0.0 | WNT7A |
Zornitza Stark gene: WNT7A was added gene: WNT7A was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: WNT7A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WNT7A were set to FUHRMANN SYNDROME; LIMB/PELVIS-HYPOPLASIA/APLASIA SYNDROME |
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| Fetal anomalies v0.0 | VPS33B |
Zornitza Stark gene: VPS33B was added gene: VPS33B was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: VPS33B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VPS33B were set to ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1 |
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| Fetal anomalies v0.0 | VIPAS39 |
Zornitza Stark gene: VIPAS39 was added gene: VIPAS39 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: VIPAS39 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VIPAS39 were set to ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2 |
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| Fetal anomalies v0.0 | UROS |
Zornitza Stark gene: UROS was added gene: UROS was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UROS were set to CONGENITAL ERYTHROPOIETIC PORPHYRIA |
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| Fetal anomalies v0.0 | TWIST1 |
Zornitza Stark gene: TWIST1 was added gene: TWIST1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TWIST1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TWIST1 were set to SAETHRE-CHOTZEN SYNDROME; CRANIOSYNOSTOSIS, TYPE 1 |
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| Fetal anomalies v0.0 | TTN |
Zornitza Stark gene: TTN was added gene: TTN was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTN were set to 29575618; 28040389; 29691892 Phenotypes for gene: TTN were set to congenital titinopathy with arthrogryposis |
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| Fetal anomalies v0.0 | TPM2 |
Zornitza Stark gene: TPM2 was added gene: TPM2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TPM2 were set to 12592607; 17339586 Phenotypes for gene: TPM2 were set to Arthrogryposis multiplex congenita, distal, type 1, 108120; Arthrogryposis, distal, type 2B, 601680; ARTHROGRYPOSIS, DISTAL, TYPE 1 Mode of pathogenicity for gene: TPM2 was set to Other |
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| Fetal anomalies v0.0 | TNNI2 |
Zornitza Stark gene: TNNI2 was added gene: TNNI2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TNNI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TNNI2 were set to Arthrogryposis multiplex congenita, distal, type 2B 601680 |
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| Fetal anomalies v0.0 | TMEM67 |
Zornitza Stark gene: TMEM67 was added gene: TMEM67 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TMEM67 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TMEM67 were set to COACH SYNDROM; JOUBERT SYNDROME TYPE 6; MECKEL SYNDROME TYPE 3; NEPHRONOPHTHISIS TYPE 11 |
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| Fetal anomalies v0.0 | THRA |
Zornitza Stark gene: THRA was added gene: THRA was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: THRA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: THRA were set to HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6 |
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| Fetal anomalies v0.0 | TCTN3 |
Zornitza Stark gene: TCTN3 was added gene: TCTN3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TCTN3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TCTN3 were set to MOHR-MAJEWSKI SYNDROME |
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| Fetal anomalies v0.0 | SON |
Zornitza Stark gene: SON was added gene: SON was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SON was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SON were set to Intellectual Disability, Congenital Malformations, and Failure to Thrive |
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| Fetal anomalies v0.0 | SMAD4 |
Zornitza Stark gene: SMAD4 was added gene: SMAD4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SMAD4 were set to JUVENILE POLYPOSIS SYNDROME; MYHRE SYNDROME; JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME |
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| Fetal anomalies v0.0 | SLC25A24 |
Zornitza Stark gene: SLC25A24 was added gene: SLC25A24 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SLC25A24 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SLC25A24 were set to Gorlin-Chaudhry-Moss syndrome (GCMS); Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction |
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| Fetal anomalies v0.0 | SGPL1 |
Zornitza Stark gene: SGPL1 was added gene: SGPL1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SGPL1 were set to Nephrotic syndrome type 14, 617575; Fetal hydrops |
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| Fetal anomalies v0.0 | SEC23B |
Zornitza Stark gene: SEC23B was added gene: SEC23B was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SEC23B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEC23B were set to 20381388 Phenotypes for gene: SEC23B were set to ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II |
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| Fetal anomalies v0.0 | SCO2 |
Zornitza Stark gene: SCO2 was added gene: SCO2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SCO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCO2 were set to 15210538; 18924171 Phenotypes for gene: SCO2 were set to FATAL INFANTILE CARDIOENCEPHALOMYOPATHY DUE TO CYTOCHROME C OXIDASE DEFICIENCY |
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| Fetal anomalies v0.0 | RBM8A |
Zornitza Stark gene: RBM8A was added gene: RBM8A was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: RBM8A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RBM8A were set to THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME |
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| Fetal anomalies v0.0 | RARB |
Zornitza Stark gene: RARB was added gene: RARB was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: RARB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: RARB were set to MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA |
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| Fetal anomalies v0.0 | PRG4 |
Zornitza Stark gene: PRG4 was added gene: PRG4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PRG4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PRG4 were set to Camptodactyly-arthropathy-coxa vara-pericarditis syndrome 208250 |
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| Fetal anomalies v0.0 | POR |
Zornitza Stark gene: POR was added gene: POR was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: POR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: POR were set to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571 |
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| Fetal anomalies v0.0 | PIEZO2 |
Zornitza Stark gene: PIEZO2 was added gene: PIEZO2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PIEZO2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: PIEZO2 were set to Ataxia, dysmetria, contractures & scoliosis with normal cognition but loss of discriminative touch perception; ARTHROGRYPOSIS, DISTAL, TYPE 3 |
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| Fetal anomalies v0.0 | NUP107 |
Zornitza Stark gene: NUP107 was added gene: NUP107 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NUP107 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NUP107 were set to EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME |
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| Fetal anomalies v0.0 | NSDHL |
Zornitza Stark gene: NSDHL was added gene: NSDHL was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NSDHL was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: NSDHL were set to CK SYNDROME; CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS |
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| Fetal anomalies v0.0 | NPHS1 |
Zornitza Stark gene: NPHS1 was added gene: NPHS1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NPHS1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHS1 were set to NEPHROTIC SYNDROME TYPE 1 |
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| Fetal anomalies v0.0 | NPHP4 |
Zornitza Stark gene: NPHP4 was added gene: NPHP4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NPHP4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHP4 were set to NEPHRONOPHTHISIS TYPE 4 |
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| Fetal anomalies v0.0 | NPHP3 |
Zornitza Stark gene: NPHP3 was added gene: NPHP3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NPHP3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHP3 were set to RENAL-HEPATIC-PANCREATIC DYSPLASIA; NEPHRONOPHTHISIS TYPE 3; MECKEL SYNDROME TYPE 7 |
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| Fetal anomalies v0.0 | NPHP1 |
Zornitza Stark gene: NPHP1 was added gene: NPHP1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NPHP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHP1 were set to NEPHRONOPHTHISIS TYPE 1; JOUBERT SYNDROME TYPE 4; SENIOR-LOKEN SYNDROME TYPE 1 |
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| Fetal anomalies v0.0 | MYRF |
Zornitza Stark gene: MYRF was added gene: MYRF was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MYRF were set to 30985895; 30070761; 31069960; 29446546; 30532227 Phenotypes for gene: MYRF were set to Congenital diaphragmatic hernia (CDH); Cardiac-urogenital syndrome, 618280; Disorders of sex development (DSD) |
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| Fetal anomalies v0.0 | MYH9 |
Zornitza Stark gene: MYH9 was added gene: MYH9 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MYH9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MYH9 were set to MAY-HEGGLIN ANOMALY; FECHTNER SYNDROME; EPSTEIN SYNDROME; MACROTHROMBOCYTOPENIA WITH PROGRESSIVE SENSORINEURAL DEAFNESS; SEBASTIAN SYNDROME; DEAFNESS AUTOSOMAL DOMINANT TYPE 17 |
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| Fetal anomalies v0.0 | MYH8 |
Zornitza Stark gene: MYH8 was added gene: MYH8 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MYH8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MYH8 were set to CARNEY COMPLEX VARIANT; DISTAL ARTHROGRYPOSIS TYPE |
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| Fetal anomalies v0.0 | MYH3 |
Zornitza Stark gene: MYH3 was added gene: MYH3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MYH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MYH3 were set to DISTAL ARTHROGRYPOSIS TYPE 2A; DISTAL ARTHROGRYPOSIS TYPE 2B |
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| Fetal anomalies v0.0 | MYBPC1 |
Zornitza Stark gene: MYBPC1 was added gene: MYBPC1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MYBPC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: MYBPC1 were set to Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4 614915 |
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| Fetal anomalies v0.0 | MAGEL2 |
Zornitza Stark gene: MAGEL2 was added gene: MAGEL2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: MAGEL2 were set to 26365340; 27195816 Phenotypes for gene: MAGEL2 were set to ARTHROGRYPOSIS MULTIPLEX CONGENITA; Schaaf-Yang syndrome, 615547; Schaaf-Yang syndrome |
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| Fetal anomalies v0.0 | LGI4 |
Zornitza Stark gene: LGI4 was added gene: LGI4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: LGI4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LGI4 were set to ARTHROGRYPOSIS MULTIPLEX CONGENITA |
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| Fetal anomalies v0.0 | KLF1 |
Zornitza Stark gene: KLF1 was added gene: KLF1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: KLF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: KLF1 were set to 28361594; 25724378 Phenotypes for gene: KLF1 were set to ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV; Hydrops Fetalis Mode of pathogenicity for gene: KLF1 was set to Other |
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| Fetal anomalies v0.0 | KANSL1 |
Zornitza Stark gene: KANSL1 was added gene: KANSL1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: KANSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: KANSL1 were set to CHROMOSOME 17Q21.31 MICRODELETION SYNDROME |
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| Fetal anomalies v0.0 | ITGA3 |
Zornitza Stark gene: ITGA3 was added gene: ITGA3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ITGA3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ITGA3 were set to INTERSTITIAL LUNG DISEASE, NEPHROTIC SYNDROME, AND EPIDERMOLYSIS BULLOSA, CONGENITAL |
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| Fetal anomalies v0.0 | INVS |
Zornitza Stark gene: INVS was added gene: INVS was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: INVS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: INVS were set to Nephronophthisis 2 602088 |
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| Fetal anomalies v0.0 | IGF2 |
Zornitza Stark gene: IGF2 was added gene: IGF2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: IGF2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Phenotypes for gene: IGF2 were set to BECKWITH-WIEDEMANN SYNDROME; CHROMOSOME 11P15.5-RELATED RUSSELL-SILVER SYNDROME |
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| Fetal anomalies v0.0 | HSD17B3 |
Zornitza Stark gene: HSD17B3 was added gene: HSD17B3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: HSD17B3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HSD17B3 were set to Pseudohermaphroditism, male, with gynecomastia 264300 |
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| Fetal anomalies v0.0 | HRAS |
Zornitza Stark gene: HRAS was added gene: HRAS was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HRAS were set to 28425981 Phenotypes for gene: HRAS were set to CONGENITAL MYOPATHY WITH EXCESS OF MUSCLE SPINDLES; COSTELLO SYNDROME |
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| Fetal anomalies v0.0 | HR |
Zornitza Stark gene: HR was added gene: HR was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: HR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HR were set to ATRICHIA WITH PAPULAR LESIONS; ALOPECIA UNIVERSALIS |
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| Fetal anomalies v0.0 | GLE1 |
Zornitza Stark gene: GLE1 was added gene: GLE1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: GLE1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GLE1 were set to ARTHROGRYPOSIS, LETHAL, WITH ANTERIOR HORN CELL DISEASE |
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| Fetal anomalies v0.0 | GLDN |
Zornitza Stark gene: GLDN was added gene: GLDN was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: GLDN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GLDN were set to Lethal arthroogryposis |
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| Fetal anomalies v0.0 | GATA6 |
Zornitza Stark gene: GATA6 was added gene: GATA6 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: GATA6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: GATA6 were set to ATRIOVENTRICULAR SEPTAL DEFECT 5; PANCREATIC AGENESIS, DIAPHRAGMATIC HERNIA AND CONGENITAL HEART DEFECTS; ATRIAL SEPTAL DEFECT 9 |
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| Fetal anomalies v0.0 | ECEL1 |
Zornitza Stark gene: ECEL1 was added gene: ECEL1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ECEL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ECEL1 were set to DISTAL ARTHROGRYPOSIS TYPE 5D |
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| Fetal anomalies v0.0 | CHRNG |
Zornitza Stark gene: CHRNG was added gene: CHRNG was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CHRNG was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHRNG were set to MULTIPLE PTERYGIUM SYNDROME ESCOBAR VARIANT |
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| Fetal anomalies v0.0 | CHRND |
Zornitza Stark gene: CHRND was added gene: CHRND was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CHRND was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHRND were set to Several associated, probably most relevant is lethal multiple pterygium syndrome 253290 |
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| Fetal anomalies v0.0 | CHRNA1 |
Zornitza Stark gene: CHRNA1 was added gene: CHRNA1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CHRNA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHRNA1 were set to 18252226; 30177536 Phenotypes for gene: CHRNA1 were set to Multiple pterygium syndrome, lethal type, 253290; MULTIPLE PTERYGIUM SYNDROME LETHAL TYPE |
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| Fetal anomalies v0.0 | CEP83 |
Zornitza Stark gene: CEP83 was added gene: CEP83 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CEP83 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CEP83 were set to INFANTILE NEPHRONOPHTHISIS AND INTELLECTUAL DISABILITY |
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| Fetal anomalies v0.0 | CEP164 |
Zornitza Stark gene: CEP164 was added gene: CEP164 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CEP164 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CEP164 were set to Nephronophthisis 15 614845 |
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| Fetal anomalies v0.0 | CDAN1 |
Zornitza Stark gene: CDAN1 was added gene: CDAN1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CDAN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CDAN1 were set to 30786798; 29668551; 29599085 Phenotypes for gene: CDAN1 were set to Anemia, congenital dyserythropoietic, type 1a, MONDO:0009135; Dyserythropoietic anemia, congenital, type Ia, OMIM:224120 |
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| Fetal anomalies v0.0 | BICD2 |
Zornitza Stark gene: BICD2 was added gene: BICD2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: BICD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: BICD2 were set to 27751653; 30054298; 29274205; 28635954 Phenotypes for gene: BICD2 were set to reduced fetal movements; PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); hydrops fetalis; Pterygium Mode of pathogenicity for gene: BICD2 was set to Other |
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| Fetal anomalies v0.0 | ASXL1 |
Zornitza Stark gene: ASXL1 was added gene: ASXL1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ASXL1 were set to BOHRING-OPITZ SYNDROME |
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| Fetal anomalies v0.0 | ASCC1 |
Zornitza Stark gene: ASCC1 was added gene: ASCC1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASCC1 were set to 28749478; 26924529; 30327447 Phenotypes for gene: ASCC1 were set to spinal muscular atrophy; hypotonia; contractures; fetal akinesia; arthrogryposis |
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| Fetal anomalies v0.0 | ADAR |
Zornitza Stark gene: ADAR was added gene: ADAR was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ADAR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: ADAR were set to AICARDI-GOUTIERES SYNDROME ASSOCIATED WITH A TYPE I INTERFERON SIGNATURE; DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1 |
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