Clinical and genetic analysis of a Chinese pedigree with autosomal recessive familial intrahepatic cholestasis type Ⅰ due to a novel variant of ATP8B1 gene
10.3760/cma.j.cn511374-20241224-00680
- VernacularTitle:ATP8B1基因新变异所致常染色体隐性家族性肝内胆汁淤积症Ⅰ型一家系的临床及遗传学分析
- Author:
Zhimin WANG
1
;
Haili QI
;
Xiaojuan WEI
;
Hualing DUAN
;
Xiaohuan LI
;
Hongyang QI
Author Information
1. 新乡市中心医院消化内科，新乡 453001
- Publication Type:Journal Article
- Keywords:
Progressive familial intrahepatic cholestasis;
Magnetic resonance imaging;
Whole exome sequencing;
ATP8B1 gene variant
- From:
Chinese Journal of Medical Genetics
2025;42(5):608-612
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation.Methods:A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241).Results:MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c. 1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c. 2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP1) and likely pathogenic (PM2_Supporting+ PM3+ PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.
