Genetic analysis of a child with Progressive familial intrahepatic cholestasis type Ⅱ due to a homozygous variant of ABCB11 gene
10.3760/cma.j.cn511374-20241028-00564
- VernacularTitle:ABCB11基因纯合变异导致进行性家族性肝内胆汁淤积症2型患儿1例的遗传学分析
- Author:
Wenbo ZHU
1
;
Xiaotai HUANG
1
;
Zhikao DENG
1
;
Cheng ZENG
1
;
Yuchen HUANG
1
;
Qiuli HUANG
1
;
Zhilan SU
1
Author Information
1. 钦州市妇幼保健院儿科一区，钦州 535099
- Publication Type:Journal Article
- Keywords:
Cholestasis;
Progressive familial intrahepatic cholestasis type Ⅱ;
Epatitis syndrome;
Jaundice;
ABCB11 gene;
Genetic mutation;
Child
- From:
Chinese Journal of Medical Genetics
2025;42(8):999-1005
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical manifestations and genetic etiology of a child with Progressive familial intrahepatic cholestasis (PFIC2).Methods:From April 2024 to June 2024, a child with jaundice, hepatomegaly and abnormal liver function who was repeatedly admitted to the First Department of Pediatrics of Qinzhou Maternal and Child Health Care Hospital was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and her parents. Genomic DNA was extracted for trio-whole exome sequencing, the candidate variant was verified by Sanger sequencing and bioinformatic analysis using REVEL, BLAST/BLAT, Swiss-Model and Swiss-Pdb Viewer software. This study was approved by the Medical Ethics Committee of the Qinzhou Maternal and Child Health Care Hospital (Ethics No.: L20240116).Results:The child was a 1.5-month-old female. Her main clinical manifestations included jaundice, hepatomegaly, brownish urine and earth-like stool. Laboratory examination showed increased levels of bilirubin, mainly direct bilirubin, increased aminotransferase, especially glutamic oxalacetic aminotransferase, accompanied by increased bile acid. Genetic testing revealed that the she has harbored a homozygous c. 3410T>G (p.V1137G) variant of the ABCB11 gene, for which both of her parents were heterozygous carriers. The variant was unreported previously, and was predicted to be pathogenic based on REVEL. Prediction with BLAST/BLAT software showed that the amino acids were highly conserved among different species. Swiss-Pdb Viewer software predicted that the variant has resulted in changes in hydrogen bonds between amino acids. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the variant was determined to be likely pathogenic (PM1+ PM2_Supporting+ PM3_Supporting+ PP3_Moderate). Conclusion:The homozygous variant of the ABCB11 gene may be the genetic cause of this child. Genetic testing is helpful for confirming the diagnosis and enrich the mutational spectrum of the ABCB11 gene.
