Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature
| Autor: | Antonio Novelli, Alfredo Di Leo, N.M. Castellaneta, Enzo Ierardi, Emanuele Agolini, Dario Cocciadiferro, Mariano Piazzolla, Leonardo Resta, Michele Barone, Loren Duda |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Hepatology medicine.diagnostic_test business.industry Benign Recurrent Intrahepatic Cholestasis Case Report Jaundice Gene mutation medicine.disease Gastroenterology 03 medical and health sciences 0302 clinical medicine Cholestasis 030220 oncology & carcinogenesis Internal medicine Liver biopsy Genetic predisposition Medicine 030211 gastroenterology & hepatology medicine.symptom ABCB11 business Cell activation |
| Zdroj: | World Journal of Hepatology. 12:64-71 |
| ISSN: | 1948-5182 |
| Popis: | 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(th) and 12(th) 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. |
| Databáze: | OpenAIRE |
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