Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature

BACKGROUND Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters. Herein, we firstly provide the evidence that a nonsense variant of ATP8B1 gene（c.1558A>T） in heterozygous form is involved in BRIC pathogenesis.CASE SUMMARY A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase. Acute and chronic liver diseases with viral, metabolic and autoimmune etiology were excluded. Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance. Liver biopsy showed: Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment, Kupffer’s cell activation/hyperplasia and preserved biliary ducts. Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria, ATP8B1 and ABCB11 gene analysis was performed. Surprisingly, we found a novel nonsense variant of ATP8B1 gene（c.1558A>T） in heterozygosis. The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation,showing a maternal inheritance. Immunohistochemistry confirmed a significant reduction of mutated gene related protein（familial intrahepatic cholestasis 1）.The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6;and 12;mo.CONCLUSION A genetic abnormality, different from those already known, could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition, thus encouraging further mutation detection in this field.