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| 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 v1.122 | DCAF15 |
Chirag Patel gene: DCAF15 was added gene: DCAF15 was added to Fetal anomalies. Sources: Other Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome Review for gene: DCAF15 was set to AMBER Added comment: ESHG 2023: 3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child) Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment. WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3). Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli. Sources: Other |
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| Fetal anomalies v1.71 | FOSL2 |
Krithika Murali gene: FOSL2 was added gene: FOSL2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FOSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOSL2 were set to 36197437 Phenotypes for gene: FOSL2 were set to Neurodevelopmental disorder, MONDO:0700092, FOSL2-related Review for gene: FOSL2 was set to GREEN Added comment: PMID 36197437 Cospain et al 2022 report 11 individuals from 10 families with heterozygous PTC variants in exon 4/4 of the FOSL2 gene. All variants were predicted to escape NMD resulting in a truncated protein, with the truncation occurring proximal to the C-terminal domain (supportive functional studies). In 10/11 families the variant occurred de novo in a single affected proband. In one family with 2 affected siblings, the variant was present in the siblings but absent in the unaffected parent likely due to gonadal mosaicism. Clinical features included: - Cutis aplasia congenital of the scalp (10/11) - Tooth enamel hypoplasia and discolouration (8/9) - Multiple other ectodermal features also noted e.g. small brittle nails, hypotrichosis/hypertrichosis, lichen sclerosis - 5 individuals had cataracts (mostly bilateral, congenital/early childhood onset) - 6/9 IUGR - 5/9 postnatal growth restriction - 7/9 developmental delay/ID - 5/7 ADHD/ASD - 2/9 seizures Sources: Literature |
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| Fetal anomalies v1.71 | ADAMTS19 | Zornitza Stark Phenotypes for gene: ADAMTS19 were changed from Heart valve disorder, MONDO:0002869 to Cardiac valvular dysplasia 2, MIM# 620067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.70 | ADAMTS19 | Zornitza Stark edited their review of gene: ADAMTS19: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.70 | ADAMTS19 | Zornitza Stark reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiac valvular dysplasia 2, MIM# 620067; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.70 | ATP7A |
Zornitza Stark changed review comment from: Well established gene-disease association, IUGR is a feature.; to: Well established gene-disease association, IUGR is a feature. Treatment: subcutaneous injections of copper histidine or copper chloride ClinGen has assessed as moderate evidence for actionability. Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms. |
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| Fetal anomalies v1.65 | ADAMTS15 | Zornitza Stark Marked gene: ADAMTS15 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.65 | ADAMTS15 | Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.65 | ADAMTS15 | Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.65 | ADAMTS15 | Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.4714 | CWF19L1 |
Krithika Murali gene: CWF19L1 was added gene: CWF19L1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CWF19L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CWF19L1 were set to 27016154 Phenotypes for gene: CWF19L1 were set to Spinocerebellar ataxia, autosomal recessive 17 - MIM#616127 Review for gene: CWF19L1 was set to GREEN Added comment: Fetal phenotype also described by 27016154 - MTOP at 22 weeks of gestation of an affected fetus due to small cerebellum and agenesis of corpus callosum. Postmortem examination showed unilateral hexadactyly and vertebral malformations. Sources: Literature |
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| Fetal anomalies v0.4677 | ADAMTS19 | Alison Yeung Phenotypes for gene: ADAMTS19 were changed from Heart valve disease (HVD) to Heart valve disorder, MONDO:0002869 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4672 | ADAMTS17 | Alison Yeung Phenotypes for gene: ADAMTS17 were changed from Weill-Marchesani 4 syndrome, recessive, 613195 to Weill-Marchesani 4 syndrome, recessive, MIM# 613195 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4480 | RBPJ | Zornitza Stark Phenotypes for gene: RBPJ were changed from ADAMS OLIVER SYNDROME to Adams-Oliver syndrome 3, MIM#614814 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4278 | ADARB1 | Zornitza Stark Marked gene: ADARB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4278 | ADARB1 | Zornitza Stark Gene: adarb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4278 | ADARB1 | Zornitza Stark Classified gene: ADARB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4278 | ADARB1 | Zornitza Stark Gene: adarb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4264 | ARPC4 |
Ain Roesley gene: ARPC4 was added gene: ARPC4 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARPC4 were set to 35047857 Phenotypes for gene: ARPC4 were set to neurodevelopmental disorder, ARPC4-related MONDO#0700092 Penetrance for gene: ARPC4 were set to Complete Review for gene: ARPC4 was set to RED gene: ARPC4 was marked as current diagnostic Added comment: post natal microcephaly except for 1 noted as 4% at birth 7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C). Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment Sources: Literature |
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| Fetal anomalies v0.4264 | ADARB1 |
Ain Roesley gene: ADARB1 was added gene: ADARB1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADARB1 were set to 32220291; 32719099 Phenotypes for gene: ADARB1 were set to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, MIM#618862 Penetrance for gene: ADARB1 were set to Complete Review for gene: ADARB1 was set to AMBER gene: ADARB1 was marked as current diagnostic Added comment: 6 unrelated families 1 microcephalic at birth (-2.2 SD) + 1 birth length at -4.3 SD Sources: Literature |
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| Fetal anomalies v0.4255 | PPP2R3C |
Chirag Patel gene: PPP2R3C was added gene: PPP2R3C was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818 Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419 Review for gene: PPP2R3C was set to GREEN Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility. Sources: Literature |
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| Fetal anomalies v0.3922 | SCN1B | Zornitza Stark Phenotypes for gene: SCN1B were changed from EPILEPSY, GENERALIZED, WITH FEBRILE SEIZURES PLUS, TYPE 1; BRUGADA SYNDROME 5 to Epileptic encephalopathy, early infantile, 52, MIM#617350; Atrial fibrillation, familial, 13, MIM# 615377 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3473 | DHH | Zornitza Stark Phenotypes for gene: DHH were changed from 46XY partial gonadal dysgenesis, with minifascicular neuropathy; 46XY sex reversal 7 to 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3400 | DHH | Belinda Chong reviewed gene: DHH: Rating: ; Mode of pathogenicity: None; Publications: 31018998, 29471294, 11017805; Phenotypes: 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.2712 | 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 v0.2494 | STRADA | Zornitza Stark Marked gene: STRADA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2494 | STRADA | Zornitza Stark Gene: strada has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2494 | STRADA | Zornitza Stark Publications for gene: STRADA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2493 | STRADA | Zornitza Stark Classified gene: STRADA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2493 | STRADA | Zornitza Stark Gene: strada has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1451 | ADA | Zornitza Stark Marked gene: ADA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1451 | ADA | Zornitza Stark Gene: ada has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1451 | ADA | Zornitza Stark Phenotypes for gene: ADA were changed from ADENOSINE DEAMINASE DEFICIENCY to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1450 | ADA | Zornitza Stark edited their review of gene: ADA: Changed phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700, MONDO:0007064 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1450 | ADA | Zornitza Stark reviewed gene: ADA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1365 | ADAMTS19 | Zornitza Stark Marked gene: ADAMTS19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1365 | ADAMTS19 | Zornitza Stark Gene: adamts19 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1365 | ADAMTS19 | Zornitza Stark Classified gene: ADAMTS19 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1365 | ADAMTS19 | Zornitza Stark Gene: adamts19 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1361 | ADAMTS19 |
Krithika Murali gene: ADAMTS19 was added gene: ADAMTS19 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ADAMTS19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS19 were set to 32323311; 31844321 Phenotypes for gene: ADAMTS19 were set to Heart valve disease (HVD) Review for gene: ADAMTS19 was set to GREEN Added comment: PMID 32323311 reports 3 additional consanguineous families (2 affected sibs in each) with anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. All 3 families had homozygous LoF variants in ADAMTS19, which segregated with disease. No functional studies. Previously reported 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert list, Literature |
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| Fetal anomalies v0.1309 | EOGT | Zornitza Stark Phenotypes for gene: EOGT were changed from ADAMS OLIVER SYNDROME to Adams-Oliver syndrome 4, MIM#615297 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1252 | NOTCH1 | Zornitza Stark Phenotypes for gene: NOTCH1 were changed from ADAMS OLIVER SYNDROME; LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION to Adams-Oliver syndrome 5 (MIM#616028) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1240 | NOTCH1 | Daniel Flanagan reviewed gene: NOTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25963545, 25132448; Phenotypes: Adams-Oliver syndrome 5 (MIM#616028); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1069 | DOCK6 | Zornitza Stark Phenotypes for gene: DOCK6 were changed from ADAMS-OLIVER SYNDROME 2 to Adams-Oliver syndrome 2, MIM#614219 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.807 | ADAMTS3 | Zornitza Stark Marked gene: ADAMTS3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.807 | ADAMTS3 | Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.807 | ADAMTS3 | Zornitza Stark Phenotypes for gene: ADAMTS3 were changed from Hennekam lymphangiectasia-lymphedema syndrome 3, OMIM:618154; Hennekam lymphangiectasia-lymphedema syndrome 3, MONDO:0032564 to Hennekam lymphangiectasia-lymphoedema syndrome 3, OMIM:618154; Hennekam lymphangiectasia-lymphoedema syndrome 3, MONDO:0032564 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.806 | ADAMTS3 | Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.806 | ADAMTS3 | Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.805 | ADAMTS3 | Zornitza Stark edited their review of gene: ADAMTS3: Changed phenotypes: Hennekam lymphangiectasia-lymphoedema syndrome 3, MIM# 618154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.805 | ADAMTS3 | Zornitza Stark edited their review of gene: ADAMTS3: Changed rating: GREEN; Changed phenotypes: Hennekam lymphangiectasia-lymphedema syndrome 3, MIM# 618154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.612 | PAX2 | Dean Phelan reviewed gene: PAX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21654726, 24676634, 31060108, 32203253; Phenotypes: Papillorenal syndrome, Renal coloboma syndrome, ventricular septal defect, skeletal deformity, ovarian teratoma, growth retardation, gout, microcephaly, developmental disorder, gonadal abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.310 | DLL4 | Zornitza Stark Phenotypes for gene: DLL4 were changed from ADAMS-OLIVER SYNDROME 6 to Adams-Oliver syndrome 6, MIM#616589 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.307 | DLL4 | Belinda Chong reviewed gene: DLL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26299364; Phenotypes: Adams-Oliver syndrome 6 MIM#616589; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.165 | ARHGAP31 | Zornitza Stark Phenotypes for gene: ARHGAP31 were changed from ADAMS-OLIVER SYNDROME 1 to Adams-Oliver syndrome 1, MIM#100300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.101 | ADAR | Zornitza Stark Marked gene: ADAR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.101 | ADAR | Zornitza Stark Gene: adar has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.100 | ADAR | Zornitza Stark Classified gene: ADAR as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.100 | ADAR | Zornitza Stark Gene: adar has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.99 | ADAR | Zornitza Stark reviewed gene: ADAR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 6, MIM# 615010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.50 | ADAMTSL2 | Zornitza Stark Marked gene: ADAMTSL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.50 | ADAMTSL2 | Zornitza Stark Gene: adamtsl2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.50 | ADAMTSL2 | Zornitza Stark Phenotypes for gene: ADAMTSL2 were changed from Geleophysic dysplasia 1 231050 to Geleophysic dysplasia 1, MIM#231050 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.49 | ADAMTSL2 | Zornitza Stark Publications for gene: ADAMTSL2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTSL2 | Zornitza Stark edited their review of gene: ADAMTSL2: Changed publications: 21415077 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTSL2 | Zornitza Stark edited their review of gene: ADAMTSL2: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTS17 | Zornitza Stark Marked gene: ADAMTS17 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTS17 | Zornitza Stark Gene: adamts17 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTS17 | Zornitza Stark reviewed gene: ADAMTS17: Rating: GREEN; Mode of pathogenicity: None; Publications: 19836009, 22486325, 24940034; Phenotypes: Weill-Marchesani 4 syndrome, recessive, MIM# 613195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTS10 | Zornitza Stark Marked gene: ADAMTS10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTS10 | Zornitza Stark Gene: adamts10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTS10 | Zornitza Stark Phenotypes for gene: ADAMTS10 were changed from Weill-Marchesani syndrome 1, recessive 277600 to Weill-Marchesani syndrome 1, recessive, MIM#277600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.47 | ADAMTS10 | Zornitza Stark Publications for gene: ADAMTS10 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | SCN1B |
Zornitza Stark gene: SCN1B was added gene: SCN1B was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: SCN1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SCN1B were set to EPILEPSY, GENERALIZED, WITH FEBRILE SEIZURES PLUS, TYPE 1; BRUGADA SYNDROME 5 |
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| Fetal anomalies v0.0 | DHH |
Zornitza Stark gene: DHH was added gene: DHH was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: DHH was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DHH were set to 46XY partial gonadal dysgenesis, with minifascicular neuropathy; 46XY sex reversal 7 |
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| Fetal anomalies v0.0 | ADA |
Zornitza Stark gene: ADA was added gene: ADA was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: ADA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ADA were set to ADENOSINE DEAMINASE DEFICIENCY |
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| Fetal anomalies v0.0 | STRADA |
Zornitza Stark gene: STRADA was added gene: STRADA was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: STRADA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STRADA were set to Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087; Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611 |
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| Fetal anomalies v0.0 | ADAMTS3 |
Zornitza Stark gene: ADAMTS3 was added gene: ADAMTS3 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS3 were set to 30450763; 28985353 Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3, OMIM:618154; Hennekam lymphangiectasia-lymphedema syndrome 3, MONDO:0032564 |
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| Fetal anomalies v0.0 | RBPJ |
Zornitza Stark gene: RBPJ was added gene: RBPJ was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: RBPJ was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RBPJ were set to 22883147; 28160419 Phenotypes for gene: RBPJ were set to ADAMS OLIVER SYNDROME |
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| Fetal anomalies v0.0 | NOTCH1 |
Zornitza Stark gene: NOTCH1 was added gene: NOTCH1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: NOTCH1 were set to ADAMS OLIVER SYNDROME; LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION |
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| Fetal anomalies v0.0 | EOGT |
Zornitza Stark gene: EOGT was added gene: EOGT was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: EOGT was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EOGT were set to ADAMS OLIVER SYNDROME |
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| Fetal anomalies v0.0 | DOCK6 |
Zornitza Stark gene: DOCK6 was added gene: DOCK6 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DOCK6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DOCK6 were set to ADAMS-OLIVER SYNDROME 2 |
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| Fetal anomalies v0.0 | DLL4 |
Zornitza Stark gene: DLL4 was added gene: DLL4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DLL4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DLL4 were set to ADAMS-OLIVER SYNDROME 6 |
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| Fetal anomalies v0.0 | ARHGAP31 |
Zornitza Stark gene: ARHGAP31 was added gene: ARHGAP31 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ARHGAP31 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ARHGAP31 were set to ADAMS-OLIVER SYNDROME 1 |
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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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| Fetal anomalies v0.0 | ADAMTSL2 |
Zornitza Stark gene: ADAMTSL2 was added gene: ADAMTSL2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ADAMTSL2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ADAMTSL2 were set to Geleophysic dysplasia 1 231050 |
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| Fetal anomalies v0.0 | ADAMTS17 |
Zornitza Stark gene: ADAMTS17 was added gene: ADAMTS17 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ADAMTS17 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS17 were set to 19836009; 22486325; 30712880; 24940034 Phenotypes for gene: ADAMTS17 were set to Weill-Marchesani 4 syndrome, recessive, 613195 |
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| Fetal anomalies v0.0 | ADAMTS10 |
Zornitza Stark gene: ADAMTS10 was added gene: ADAMTS10 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ADAMTS10 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ADAMTS10 were set to Weill-Marchesani syndrome 1, recessive 277600 |
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