Identification of a novel c.3080delC JAG1 gene mutation associated with Alagille syndrome by whole-exome sequencing (Preprint)

BACKGROUND Alagille syndrome is an autosomal dominant disorder associated with variable clinical phenotypic features including cholestasis, congenital heart defects, vertebral defects, and dysmorphic facies. OBJECTIVE Whole-exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new opportunities for mutations/genes identification. METHODS Next-generation sequencing (NGS) - Whole-exome sequencing was used to identify pathogenic variants of the proband. In this paper, we have uncovered a novel JAG1 mutation associated with Alagille syndrome in a 5 years old girl presented with conjugated hyperbilirubinemia and infantile cholestasis. RESULTS The exome sequencing analysis revealed the presence of a novel JAG1 heterozygous c.3080delC variant in exon 25. The detected mutation determines a stop codon (p.P1027RfsTer9) in the gene sequence, encoding a truncated protein. Our exome observations were confirmed through Sanger sequencing as well. CONCLUSIONS Here, we report a case of a patient diagnosed with Alagille syndrome, and our finding emphasis the detection of novel JAG1 mutation associated with Alagille syndrome variants thereby, establishing the genetic diagnosis of the disease. CLINICALTRIAL N/A