A study of exons 14, 15, and 24 of the ABCB11 gene in Egyptian children with normal GGT cholestasis

Progressive familial intrahepatic cholestasis is a heterogeneous group of rare autosomal recessive disorders associated with bile acid secretion or transport defects and presents with intrahepatic cholestasis. They usually develop in infancy and childhood and result in either end-stage liver disease and death or liver transplantation in infancy to adulthood [1]. Beyond the classically recognized PFIC1 (Byler disease), PFIC2 (bile salt export pump [BSEP] deficiency), and PFIC3 (MDR3 deficiency), sequencing studies have recently identified new gene mutations associated with previously unexplained cases, thus expanding the disease spectrum to PFIC4 (TJP2 deficiency), PFIC5 (related to NR1H4), and MYO5B-associated cholestasis [2], [3], [4].

PFIC2 is caused by mutations in the ATP-binding cassette subfamily B member 11 gene (ABCB11), which encodes the BSEP protein (1321–amino acid) and is the main transporter of bile acids from hepatocytes to the canalicular lumen against a concentration gradient [1]. It is composed of 27 coding exons and a leading untranslated exon, spans a 108 kb genomic region, and is located on chromosome 2q31.1 [5]. This transporter protein is expressed at the canalicular membrane of hepatocytes [6].

The BSEP disease spectrum can vary from benign recurrent intrahepatic cholestasis to severe cholestasis, pruritus, growth failure, and fat-soluble vitamin deficiency with rapidly progressing chronic liver disease, and possible risk of hepatocellular carcinoma [7]. The biochemical features of PFIC2 characteristically show low or normal levels of gamma-glutamyl transpeptidase (GGT) with elevated levels of serum bile acid and extremely low biliary bile acid concentration [8]. Genotyping of the ABCB11 gene variations is the gold standard for diagnosis and involves DNA sequencing of the coding exons of the ABCB11 gene [6]. A genotype–phenotype correlation exists and partly explains the disease variability [9]. For both diagnostic and prognostic purposes, genetics has largely replaced immunohistochemistry [7].

The present study aimed to investigate the possible association of the variations in exons 14, 15, and 24 of the ABCB11 gene as a cause of PFIC2 among a selected group of Egyptian patients.

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