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| Congenital Heart Defect v0.347 | JAG1 | Zornitza Stark Marked gene: JAG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.347 | JAG1 | Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.347 | JAG1 | Zornitza Stark Phenotypes for gene: JAG1 were changed from to Alagille syndrome 1 #118450 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.346 | JAG1 | Zornitza Stark Publications for gene: JAG1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.345 | JAG1 | Zornitza Stark Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.315 | JAG1 | Uditi Shah reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26580007, 19325125, 11139239, 9207787, 9585603, 11152664, 32065591, 12022040, 20437614, 36400760); Phenotypes: ?Deafness, congenital heart defects, and posterior embryotoxon #617992, Alagille syndrome 1 #118450, Charcot-Marie-Tooth disease, axonal, type 2HH #619574, Tetralogy of Fallot #187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.315 | JAG1 | Uditi Shah Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.315 | JAG1 |
Uditi Shah changed review comment from: JAG1 is a gene that plays a crucial role in capillary morphogenesis, mesenchymal stem cell differentiation into cardiomyocytes, and the regulation of signaling pathways such as Notch and Wnt. Mutations in the JAG1 gene are associated with Alagille Syndrome (ALGS), a disorder characterized by liver, heart, and other organ abnormalities. ALGS exhibits high genetic heterogeneity, with various types of mutations identified, including deletions, insertions, splice site mutations, and missense mutations. The majority of ALGS cases involve haploinsufficiency, where a single functional copy of the JAG1 gene is insufficient for normal development. However, some missense mutations may act in a dominant-negative manner, inhibiting Notch signaling. In TOF, a missense mutation in JAG1 was identified in a kindred segregating autosomal dominant TOF with variable expressivity and characteristic facial features. JAG1 mutations in axonal Charcot-Marie-Tooth disease type 2HH were associated with impaired peripheral nerve integrity and altered Notch signaling. Another syndrome, DCHE, involving hearing loss, congenital heart defects, and posterior embryotoxon, was also linked to a JAG1 missense mutation. (PMID: 12022040 PMID: 20437614 PMID: 36400760); to: JAG1 is a gene that plays a crucial role in capillary morphogenesis, mesenchymal stem cell differentiation into cardiomyocytes, and the regulation of signaling pathways such as Notch and Wnt. (PMID: 26580007, PMID: 19325125) Mutations in the JAG1 gene are associated with Alagille Syndrome (ALGS), a disorder characterized by liver, heart, and other organ abnormalities. ALGS exhibits high genetic heterogeneity, with various types of mutations identified, including deletions, insertions, splice site mutations, and missense mutations. The majority of ALGS cases involve haploinsufficiency, where a single functional copy of the JAG1 gene is insufficient for normal development. However, some missense mutations may act in a dominant-negative manner, inhibiting Notch signaling. (PMID: 11139239, PMID: 9207787, PMID: 9585603) In TOF, a missense mutation in JAG1 was identified in a kindred segregating autosomal dominant TOF with variable expressivity and characteristic facial features. (PMID: 11152664) JAG1 mutations in axonal Charcot-Marie-Tooth disease type 2HH were associated with impaired peripheral nerve integrity and altered Notch signaling. (PMID: 32065591) Another syndrome, DCHE, involving hearing loss, congenital heart defects, and posterior embryotoxon, was also linked to a JAG1 missense mutation. (PMID: 12022040 PMID: 20437614 PMID: 36400760) |
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| Congenital Heart Defect v0.315 | JAG1 | Uditi Shah reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12022040 PMID: 20437614 PMID: 36400760; Phenotypes: ?Deafness, congenital heart defects, and posterior embryotoxon #617992, Alagille syndrome 1 #118450, Charcot-Marie-Tooth disease, axonal, type 2HH #619574, Tetralogy of Fallot #187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.163 | MIB1 |
Zornitza Stark changed review comment from: Established congenital cardiac disease gene. PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 11 de novo variants (1 frameshift, 2 missense, 2 splice acceptor, 1 splice donor, 5 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Expert Review; to: Li 2018 (PMID: 30322850): - in 4 CHD patients: p.Q237H (gv2v3 absent), p.W271G (gv2v3 absent), p.S520R (v2 5 hets) and p.T312Kfs*55 (NMD-pred, absent but many comparables in gnomAD). - HEK293T cells transfection studies showed: T312Kfs*55 and W271G strongly impaired MIB1 function on substrate ubiquitination, while Q237H and S520R had slight or no obvious changes. Interaction between MIB1 and JAG1 is severely interrupted by p.T312Kfs*55 and p.W271G, but not really in the other 2 missense. - Overexpression of wt or mutant in zebrafish all resulted in dysmorphic pheno, therefore not informative. PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 11 de novo variants (1 frameshift, 2 missense, 2 splice acceptor, 1 splice donor, 5 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Expert Review |
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| Congenital Heart Defect v0.0 | JAG1 |
Zornitza Stark gene: JAG1 was added gene: JAG1 was added to Congenital Heart Defect_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: JAG1 was set to Unknown |
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