Alagille syndrome due to a novel JAG1 mutation in a Chinese pediatric patient: A case report.

RATIONALE: Alagille syndrome (ALGS) is a multisystem autosomal dominant disease with variable expressivity and phenotypic penetrance, characterized by abnormalities in liver, heart, skeleton, eyes, kidneys, face, and vasculature. Mutations in JAG1 are the major genetic cause of ALGS. Here, we illustrated the clinical and genetic characteristics of a pediatric ALGS case caused by a novel JAG1 mutation, aiming to strengthen clinicians' awareness and understanding of ALGS at clinical and molecular levels. PATIENT CONCERNS: A 5-year-old Chinese female presented with suspected ALGS clinical phenotypes including chronic cholestasis, liver dysfunction, and pulmonary artery stenosis. DIAGNOSES: A novel heterozygous missense mutation (c.3112C†>†G, p.L1038V) in the exon 25 of the JAG1 gene was identified in this patient via whole-exome sequencing. Nucleotide sequence conservation analysis showed that the novel JAG1 c.3112C†>†G mutation was located in evolutionarily conserved region, suggesting its potential importance to the function of JAGGED1 protein encoded by JAG1. Subsequently, pathogenicity of this novel mutation was further confirmed by flow cytometry which demonstrated a defective expression of wild-type JAGGED1 protein. Combining the clinical features with genetic findings, this patient was eventually diagnosed as ALGS. INTERVENTIONS: Patient received supportive treatments, including blood transfusion, vitamin K1 supplementation, and the application of liver-protection drugs. OUTCOMES: This patient developed liver failure during hospitalization. Regrettably, the guardians gave up further therapies (blood purification therapy and liver transplantation) for the patient and asked to be discharged. Soon after, the patient died at home due to deterioration of her condition. LESSONS: In the present study, a novel pathogenic JAG1 mutation was identified using whole-exome sequencing in a Chinese patient with ALGS phenotype, expanding the mutational spectrum of JAG1 gene.