Identification of a Novel c.3080delC JAG1 Gene Mutation Associated With Alagille Syndrome: Whole Exome Sequencing

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 possibilities for mutations or genes identification. Methods WES was used to identify pathogenic variants, which may have significant prognostic implications for patients’ clinical presentation of the proband. In this paper, we have uncovered a novel JAGGED1 gene (JAG1) mutation associated with Alagille syndrome in a 5-year-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 variant introduced 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, conjugated hyperbilirubinemia, and infantile cholestasis, with emphasis on its association with the detection of the novel JAG1 mutation, thereby establishing the genetic diagnosis of the disease.