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| Congenital Heart Defect v0.241 | FOXP1 | Zornitza Stark Marked gene: FOXP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.241 | FOXP1 | Zornitza Stark Gene: foxp1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.241 | FOXP1 | Zornitza Stark Phenotypes for gene: FOXP1 were changed from Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome to Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670; Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.240 | FOXP1 | Zornitza Stark Classified gene: FOXP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.240 | FOXP1 | Zornitza Stark Gene: foxp1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.239 | FOXP1 | Zornitza Stark reviewed gene: FOXP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.239 | FOXP1 |
Chloe Stutterd gene: FOXP1 was added gene: FOXP1 was added to Congenital Heart Defect. Sources: Literature,Expert list Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXP1 were set to 29090079; 23766104 Phenotypes for gene: FOXP1 were set to Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome Review for gene: FOXP1 was set to AMBER gene: FOXP1 was marked as current diagnostic Added comment: Best evidence of association with CHD comes from PMID:29090079 but only for two patients and one with very mild CHD only. Study is a prospective investigation of nine children with FOXP1 syndrome using a battery of standardized clinical assessments, two had CHD (one with pulmonary stenosis, the other with self-resolving PDA). Authors recommend cardiac screening for patients with FOXP1 neurodevelopmental syndrome. PMID:23766104: Single patient with CHD (AVSD, hypoplastic left ventricle and aortic arch, left atrioventricular valve stenosis, bilateral superior vena cavae, transposed great vessels) and cryptorchidism and a novel 3p14 microdeletion involving first 4 exons of FOXP1, inherited from an unaffected mother. FOXP1 sequenced in 82 patients with AVSD or HLHS: 2/82 patients had FOXP1 variant c.1702C>T;p.(Pro568Ser), inheritance unknown, variant present gnomAD in 153 hets, benign/likely benign in ClinVar . PMID: 25908055; 22290856: CHD associated with 3p14 contiguous gene deletion syndrome involving FOXP1 and up to 30 other genes. Homozygous null mice have CHD (MGI ID:1914004; PMID: 15342473). Sources: Literature, Expert list |
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| Congenital Heart Defect v0.128 | ZMYM2 |
Zornitza Stark gene: ZMYM2 was added gene: ZMYM2 was added to Congenital Heart Defect. Sources: Expert Review Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZMYM2 were set to 32891193 Phenotypes for gene: ZMYM2 were set to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM# 619522 Review for gene: ZMYM2 was set to GREEN Added comment: Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants. Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly. 14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family. The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT. ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body). It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors. The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT). Sources: Expert Review |
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