Bile salt export pump deficiency: A de novo mutation in a child compound heterozygous for ABCB11. Laboratory investigation to study pathogenic role and transmission of two novel ABCB11 mutations. Issue 3 (26th February 2013)

• Record Type: Journal Article
• Authors: Francalanci, Paola; Giovannoni, Isabella; Candusso, Manila; Bellacchio, Emanuele; Callea, Francesco
• Is Part Of: Hepatology research. Volume 43:Issue 3(2013:Mar.)
• Page Start: 315
• Page End: 319
• Publication Date: 2013-02-26
• Subjects: Liver -- Diseases -- Periodicals; Liver Diseases -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1111/j.1872-034X.2012.01061.x
• Languages: English
• ISSNs: 1386-6346

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal disorders. PFIC type 2 is due to mutation in <italic>ABCB11</italic>, the gene encoding the bile salt export pump (BSEP) protein. The aim of the study was to describe a child with a de novo mutation in a compound heterozygous for <italic>ABCB11</italic> gene. We report a 1.7‐year‐old girl who presented with pruritus, jaundice and liver dysfunction of PFIC type 2. Immunohistochemistry and molecular analysis are described. Liver biopsy showed micronodular cirrhosis and immunohistochemical staining for BSEP, the protein encoded by ABCB11, displayed a patchy and faint reactivity. Molecular analysis revealed two novel mutations of <italic>ABCB11.</italic> We give details that one mutation is transmitted by the mother while the second one appears a de novo mutation as mutations or a potential mosaicism were ruled out in the natural father. We further speculate that the <italic>ABCB11</italic> mutations do not prevent BSEP glycoprotein to be expressed at the canalicular pole of hepatocytes, but interfere with its ability to export bile salts. As in most instances, mutational analysis is performed following the histochemical demonstration of an undetectable BSEP on liver biopsy specimen. This case stresses that clinical PFIC with an attenuated rather than absent BSEP immunostaining can still be due to <italic>ABCB11</italic> mutations presumably encoding a functionally deficient protein.</p> </abstract>