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| Fetal anomalies v1.208 | DOHH |
Ain Roesley changed review comment from: 4 families - 5 affecteds 1x cardiomyopathy at prenatal examination 4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc microcephaly was post-natal Sources: Literature; to: 4 families - 5 affecteds prenatal examination: 1x cardiomyopathy 1x increased nuchal translucency; chylothorax post-natal: 4/5 presented with CHD - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc 5/5 microcephaly |
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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 v1.58 | KIF5B |
Chirag Patel gene: KIF5B was added gene: KIF5B was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF5B were set to PMID: 35342932 Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM # Review for gene: KIF5B was set to GREEN Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants. Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages. Sources: Literature |
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| Fetal anomalies v1.15 | MDFIC |
Belinda Chong gene: MDFIC was added gene: MDFIC was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MDFIC were set to 35235341 Phenotypes for gene: MDFIC were set to Hydrops fetalis MONDO:0015193 Review for gene: MDFIC was set to GREEN Added comment: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. Seven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax. Sources: Literature |
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| Fetal anomalies v0.4559 | PNKP | Zornitza Stark Phenotypes for gene: PNKP were changed from ATAXIA-OCULOMOTOR APRAXIA 4; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 10 to Microcephaly, seizures, and developmental delay, MIM#613402 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4483 | RAX | Zornitza Stark Marked gene: RAX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4483 | RAX | Zornitza Stark Gene: rax has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4483 | RAX | Zornitza Stark Phenotypes for gene: RAX were changed from MICROPHTHALMIA ISOLATED TYPE 3 to Microphthalmia, isolated 3, MIM# 611038 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4482 | RAX | Zornitza Stark Publications for gene: RAX were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3681 | GRIN2A |
Zornitza Stark changed review comment from: Large cohort of 248 individuals reported in PMID: 30544257: The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. Pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes. Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function.; to: Large cohort of 248 individuals reported in PMID: 30544257: The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. Pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes. Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. Clinical presentation is typically postnatal. |
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| Fetal anomalies v0.3484 | SEMA3A |
Krithika Murali gene: SEMA3A was added gene: SEMA3A was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SEMA3A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: SEMA3A were set to 28075028; 33369061; 20301509; 21059704; 24124006; 22927827 Phenotypes for gene: SEMA3A were set to {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease Review for gene: SEMA3A was set to GREEN Added comment: Heterozygous variants associated with isolated GnRH deficiency with or without anosmia (Kallman syndrome like). Anomalies such as unilateral renal aplasia which can be detected antenatally reported with Kallman syndrome but not published with heterozygous SEMA3A variants. More severe phenotype with biallelic SEMA3A variants reported with features detectable antenatally. PMID 33369061 Gileta et al 2021 - report x1 patient. Female proband was compound heterozygote for a nonsense variant and a multiexonic deletion of SEMA3A. Presents with postnatal short stature, congenital cardiac anomalies, dysmorphic features, hypogonadotrophic hypogonadism and anosmia. PMID 28075028 Baumann et al 2017 - report x1 patient. Homozygous LoF variants identified in a proband from a consanguineous Turkish family. Noted at birth to have a high-positioned scapulae, deformed ribs and a lateral clavicular hook. The patient also had upper/lower limb contractures and aberrant right subclavian artery. Mild facial dysmorphism, micropenis and hypogonadotrophic hypogonadism also noted in the first week of life. Postnatal short stature (length 50cm at term birth) PMID 24124006 Hofmann et al 2013 - first reported biallelic variants in a proband with postnatal short stature, skeletal anomalies of the thorax, congenital heart defect and camptodactyly Sources: Literature |
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| Fetal anomalies v0.1626 | APTX | Zornitza Stark Phenotypes for gene: APTX were changed from ATAXIA WITH OCULOMOTOR APRAXIA 1 to Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia, MIM#208920 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1625 | APTX | Zornitza Stark edited their review of gene: APTX: Changed phenotypes: Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia, MIM#208920 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1453 | AFF2 | Zornitza Stark Phenotypes for gene: AFF2 were changed from FRAGILE X-E MENTAL RETARDATION SYNDROME to Mental retardation, X-linked, FRAXE type 309548 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1211 | CHD3 | Zornitza Stark Phenotypes for gene: CHD3 were changed from Apraxia of speech to Snijders Blok-Campeau syndrome, MIM#618205 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | GDF2 |
Zornitza Stark gene: GDF2 was added gene: GDF2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: GDF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GDF2 were set to 32618121 Phenotypes for gene: GDF2 were set to hydrops; hydrothorax; Lymphatic dysplasia |
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| Fetal anomalies v0.0 | APTX |
Zornitza Stark gene: APTX was added gene: APTX was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: APTX was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: APTX were set to ATAXIA WITH OCULOMOTOR APRAXIA 1 |
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| Fetal anomalies v0.0 | CHD3 |
Zornitza Stark gene: CHD3 was added gene: CHD3 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CHD3 were set to Apraxia of speech |
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| Fetal anomalies v0.0 | RAX |
Zornitza Stark gene: RAX was added gene: RAX was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: RAX was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RAX were set to MICROPHTHALMIA ISOLATED TYPE 3 |
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| Fetal anomalies v0.0 | PNKP |
Zornitza Stark gene: PNKP was added gene: PNKP was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PNKP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PNKP were set to ATAXIA-OCULOMOTOR APRAXIA 4; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 10 |
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