Alagille syndrome caused by p.L2014Vfs*10 in NOTCH2: a case report and review of the literature.

backgroundAlagille syndrome is an autosomal dominant disorder caused by pathogenic variants in JAG1 or NOTCH2, which encode fundamental components of the Notch signaling pathway. Genotype-phenotype correlation studies have not yet shown associations between mutation type and clinical manifestations or severity. Medical management is supportive, focusing on clinical manifestations of the disease. CASE PRESENTATION: In the present study, a 3.5-month-old Chinese female child of Han nationality with retarded growth, cholestasis, and hepatic function damage was diagnosed with Alagille syndrome. To determine the cause, whole-exome sequencing was carried out. p.L2014Vfs*10, a novel frameshift variation of NOTCH2 caused by two-base-pair deletion at 6040 and 6041 was found and confirmed as inherited from the mother. The clinical diagnosis and treatment process are described in detail.

conclusionEarly diagnosis of Alagille syndrome is difficult, and it is prone to misdiagnosis as biliary atresia. We describe herein a case characterized by cholestatic liver disease in the Chinese context. The whole process of the occurrence, development, clinical diagnosis, and treatment is described in detail, providing guidelines for the management of similar diseases, along with a novel variation to improve the variation profile of NOTCH2, for better understanding of the pathogenesis of Alagille syndrome.