Congenital Heart Defect

Gene: JAG1

Green List (high evidence)

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

• PMID: 26580007
• 19325125
• 11139239
• 9207787
• 9585603
• 11152664
• 32065591
• 12022040
• 20437614
• 36400760)