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| Fetal anomalies v1.300 | PDE12 |
Zornitza Stark gene: PDE12 was added gene: PDE12 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE12 were set to 39567835 Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970, PDE12-related Review for gene: PDE12 was set to GREEN Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death). -Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle. -Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron transfer chain activities in fibroblasts. -Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V). WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity. PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein. Sources: Literature |
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| Fetal anomalies v1.245 | BCORL1 | Zornitza Stark Marked gene: BCORL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.245 | BCORL1 | Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.245 | BCORL1 | Zornitza Stark Classified gene: BCORL1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.245 | BCORL1 | Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.244 | BCORL1 |
Zornitza Stark gene: BCORL1 was added gene: BCORL1 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: BCORL1 were set to Congenital anomaly of the kidney and urinary tract, MONDO:0019719, BCORL1-related Review for gene: BCORL1 was set to AMBER Added comment: Emerging evidence of disease association. Sources: Expert Review |
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| Fetal anomalies v0.3564 | RIN2 | Zornitza Stark changed review comment from: Macrocephaly, subcortical cysts and other brain abnormalities are a feature.; to: Macrocephaly, subcortical cysts and other brain abnormalities are a feature. More than 5 unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3564 | RIN2 | Zornitza Stark changed review comment from: ID is not a key feature of this syndrome, most individuals described as having normal/borderline intellect.; to: Macrocephaly, subcortical cysts and other brain abnormalities are a feature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.2674 | PAFAH1B1 | Zornitza Stark Phenotypes for gene: PAFAH1B1 were changed from SUBCORTICAL BAND HETEROTOPIA; LISSENCEPHALY TYPE 1 to Lissencephaly 1, MIM# 607432; Subcortical laminar heterotopia, MIM# 607432; MONDO:0011830 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.820 | DCX | Zornitza Stark Phenotypes for gene: DCX were changed from LISSENCEPHALY X-LINKED TYPE 1; SUBCORTICAL BAND HETEROTOPIA X-LINKED to Lissencephaly, X-linked, MIM# 300067; Subcortical laminal heterotopia, X-linked 300067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.818 | DCX | Zornitza Stark changed review comment from: Well established gene-disease association.; to: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.818 | DCX | Zornitza Stark edited their review of gene: DCX: Changed phenotypes: Lissencephaly, X-linked, MIM# 300067, Subcortical laminal heterotopia, X-linked 300067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.627 | MLC1 | Zornitza Stark Phenotypes for gene: MLC1 were changed from LEUKOENCEPHALOPATHY MEGALENCEPHALIC WITH SUBCORTICAL CYSTS to Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.582 | MLC1 | Daniel Flanagan reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11254442, 18757878, 16652334; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.302 | BCOR | Zornitza Stark Marked gene: BCOR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.302 | BCOR | Zornitza Stark Gene: bcor has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.302 | BCOR | Zornitza Stark Phenotypes for gene: BCOR were changed from MICROPHTHALMIA SYNDROMIC TYPE 2 to Microphthalmia, syndromic 2, MIM# 300166; Oculofaciocardiodental syndrome; Lenz microphthalmia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.301 | BCOR | Zornitza Stark Publications for gene: BCOR were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | PAFAH1B1 |
Zornitza Stark gene: PAFAH1B1 was added gene: PAFAH1B1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PAFAH1B1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PAFAH1B1 were set to SUBCORTICAL BAND HETEROTOPIA; LISSENCEPHALY TYPE 1 |
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| Fetal anomalies v0.0 | MLC1 |
Zornitza Stark gene: MLC1 was added gene: MLC1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MLC1 were set to LEUKOENCEPHALOPATHY MEGALENCEPHALIC WITH SUBCORTICAL CYSTS |
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| Fetal anomalies v0.0 | DCX |
Zornitza Stark gene: DCX was added gene: DCX was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DCX 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: DCX were set to LISSENCEPHALY X-LINKED TYPE 1; SUBCORTICAL BAND HETEROTOPIA X-LINKED |
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| Fetal anomalies v0.0 | BCOR |
Zornitza Stark gene: BCOR was added gene: BCOR was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: BCOR 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: BCOR were set to MICROPHTHALMIA SYNDROMIC TYPE 2 |
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