Syndromic Retinopathy

Gene: JAG1

I don't know

Thoracic aortic aneurysm appears to be a rare feature of Alagille syndrome, but has been reported as a presenting feature in at least 2 families
PMID: 35819173 - two families segregating JAG1 variants that present with isolated aneurysmal disease lacking other Alagille syndrome (AGS) clinical characteristics (such as the hepatic abnormalities, posterior embryotoxon, and cardiac structural changes). Histological evaluation of aortic tissue from one of the TAA cases revealed elastin degradation and abnormal collagen deposition.
PMID: 30071989 - JAG1 assessed as no (clinical) evidence for HTAAD by the ClinGen Heritable Thoracic Aortic Aneurysm and Dissection GCEP in 2018. Currently under review
PMID: 14993126 - three AGS patients with aortic aneurysms and 2 with aortic coarctations identified in a retrospective chart review of 268 AGS individuals autopsy finding in three patients who died of sudden death
PMID: 18570795 - 17 yo asymptomatic AGS case with dilatation of the ascending aorta from the root identified

Created: 9 Sep 2022, 12:19 a.m. | Last Modified: 9 Sep 2022, 12:19 a.m.

Panel Version: 1.323

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
thoracic aortic aneurysm MONDO:0005396

Publications

• 35819173
• 30071989
• 14993126
• 18570795

Green List (high evidence)

Association with Alagille is very well established.

Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature

Created: 23 Apr 2020, 10:19 a.m. | Last Modified: 7 Mar 2022, 1:56 a.m.

Panel Version: 0.11163

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Alagille syndrome 1, MIM# 118450; Charcot-Marie-Tooth disease, axonal, type 2HH, MIM# 619574

Publications

• 32065591
• 25707699