Novel ATP8B1 gene mutation in a family with progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) denotes a rare, heterogeneous group of hepatobiliary disorders with autosomal recessive inheritance. PFIC 1 results from a genetic mutation involving the ATP8B1 gene on chromosome 18. It classically manifests with infantile-onset cholestasis with pruritus and malabsorption, progressing to hepatic failure in the first decade of life. There are a few other minor manifestations described previously in the literature. We report two siblings with varying clinical presentations of a fatal hepatic disease. Carrier whole-exome sequencing detected a novel heterozygous pathogenic mutation in the exon 28 of the ATPBB1 gene in both parents, thus validating the diagnosis of PFIC 1.