Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Arab J Gastroenterol. 2022 Feb;23(1):15-19. doi: 10.1016/j.ajg.2021.11.003. Epub 2022 Feb 10.
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.
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.
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.
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.
进行性家族性肝内胆汁淤积症 2 型（PFIC2）是一种罕见的遗传性疾病，由 ATP 结合盒亚家族 B 成员 11 基因（ABCB11）的突变引起，该基因编码胆汁盐输出泵（BSEP），是将胆汁盐从肝细胞分泌到胆小管腔的主要转运体。BSEP 合成和/或功能缺陷导致胆汁盐分泌减少，随后在肝细胞中积聚胆汁盐并导致肝细胞损伤。本研究旨在检测一组埃及婴儿和儿童中疑似 PFIC2 患者 ABBC11 基因外显子 14、15 和 24 的变异，这些患者的 γ-谷氨酰转肽酶（GGT）正常胆汁淤积。
这项观察性病例对照研究共纳入 13 名疑似 PFIC2 的儿童患者和 13 名健康对照者。通过 DNA 提取、PCR 扩增、纯化，然后对 ABBC11 基因外显子 14、15 和 24 进行测序分析，对 ABCB11 基因进行基因分型。
研究检测到两个单核苷酸变异，外显子 14 中的 c.1638+32T>C（rs2241340）和外显子 24 中的 c.3084A>G（p.Ala1028=）（rs497692）。在外显子 15 中未发现变异。
本研究揭示了涉及 ABBC11 基因外显子 14 和 24 的两个良性变异。外显子 14、15 和 24 不是埃及 PFIC2 患者常见突变的热点。需要进一步研究 ABBC11 基因的其他外显子以确认 PFIC2 的诊断。
