[Analysis of a novel JAG1 variant and clinical phenotype in a family affected with Alagille syndrome].

Objective: To explore the genetic basis of a pedigree affected with Alagille syndrome (ALGS).

Methods: Targeted capture and next generation sequencing was carried out for the proband. Candidate variants were verified by Sanger sequencing among his family members. Their pathogenicity of the variant was predicted with bioinformatic analysis. Clinical characteristics and genotype-phenotype correlation were analyzed.

Results: The proband, his elder sister and mother were found to carry a heterozygous c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene, which may lead to premature termination of translation and a truncated protein with loss of function. The variant was unreported previously. The phenotypes of the proband (cholestasis, pulmonary artery stenosis and peculiar faces) have differed from those of his elder sister (cholestasis with pruritus, posterior embryonic ring of cornea) and mother (with no clinical manifestation). Cholestasis and peculiar face of the proband became insignificant with age.

Conclusion: The c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene probably underlay the ALGS in this pedigree with incomplete penetrance.