Congenital Heart Defect
Gene: JAG1
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)
Given the strong association this gene has with ALGS and TOF which are Congenital Heart Defects, and evidence supporting its association with hearing loss, and posterior embryotoxon, JAG1 is marked green on this panel. (PMID: 12022040 PMID: 20437614, PMID: 36400760)Created: 20 Nov 2023, 4:48 a.m. | Last Modified: 20 Nov 2023, 4:48 a.m.
Panel Version: 0.315
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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
Publications
Gene: jag1 has been classified as Green List (High Evidence).
Phenotypes for gene: JAG1 were changed from to Alagille syndrome 1 #118450
Publications for gene: JAG1 were set to
Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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