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

Background and study aims: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rare inherited disorder caused by mutation in the ATP-binding cassette subfamily B member 11 gene (ABCB11) that encodes the bile salt export pump (BSEP), which is the main transporter of bile acids from hepatocytes to the canalicular lumen. Defects in BSEP synthesis and/or function lead to reduced bile salt secretion followed by accumulation of bile salts in hepatocytes and hepatocellular damage. This study aimed to detect variations in exons 14, 15, and 24 of the ABCB11 gene in patients with suspected PFIC2 among a group of Egyptian infants and children with normal gamma-glutamyl transpeptidase (GGT) cholestasis. Patients and methods: This observational case-control study was conducted on 13 children with suspected PFIC2 and 13 healthy subjects as controls. Genotyping of the ABCB11 gene was performed via DNA extraction followed by PCR amplification, purification, and then sequencing analysis of exons 14, 15, and 24 of the ABCB11 gene. Results: The study detected two single nucleotide variations, c.1638+ 32T > C (rs2241340) in exon 14 and c.3084A > G (p.Ala1028 = ) (rs497692) in exon 24 of the ABCB11 gene. No variations were identified in exon 15. Conclusion: The study revealed two benign variants involving exons 14 and 24 of the ABCB11 gene. Exons 14, 15, and 24 are not hot spots for common mutations in Egyptian PFIC2 patients. Further study of other exons of the ABCB11 gene is necessary to confirm the diagnosis of PFIC2. (c) 2021 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Automated summary

This study aimed to detect variations in exons 14, 15, and 24 of the ABCB11 gene in Egyptian infants and children with suspected PFIC2. Two variations were found in exons 14 and 24, while no variations were identified in exon 15. This suggests that exons 14, 15, and 24 are not hot spots for common mutations in Egyptian PFIC2 patients.