Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2025; 31(14): 104975
Published online Apr 14, 2025. doi: 10.3748/wjg.v31.i14.104975
Clinical, genetic and functional perspectives on ATP-binding cassette subfamily B member 4 variants in five cholestasis adults
Yu-Hang Weng, Yu-Feng Zheng, Dan-Dan Yin, Qing-Fang Xiong, Jin-Long Li, Shun-Xin Li, Wei Chen, Yong-Feng Yang
Yu-Hang Weng, Yu-Feng Zheng, Qing-Fang Xiong, Yong-Feng Yang, Department of Hepatology, The Second Hospital of Nanjing, The Affiliated to Nanjing University of Chinese Medicine, The Affiliated to Southeast University Medical School, Nanjing 210003, Jiangsu Province, China
Dan-Dan Yin, Shun-Xin Li, Wei Chen, Clinical Research Center, The Second Hospital of Nanjing, The Affiliated to Nanjing University of Chinese Medicine, The Affiliated to Southeast University Medical School, Nanjing 210003, Jiangsu Province, China
Jin-Long Li, Department of Medical Laboratory, The Second Hospital of Nanjing, The Affiliated to Nanjing University of Chinese Medicine, The Affiliated to Southeast University Medical School, Nanjing 210003, Jiangsu Province, China
Co-corresponding authors: Wei Chen and Yong-Feng Yang.
Author contributions: Weng YH collected all clinical data, conducted all experiments, analyzed all the data, and wrote the initial manuscript draft; Zheng YF assisted in collecting clinical data and conducting experiments; Yin DD guided the in vitro experiments methods and steps; Xiong QF assisted in collecting clinical data and provided guidance; Li JL guided plasmid construction and synthesis of missense variants; Li SX assisted in conducting some in vitro experiments. As co-corresponding authors, Chen W and Yang YF played pivotal and indispensable roles in the experimental design, data interpretation, and manuscript preparation. The funding for this project was applied for and obtained by Yang YF, while Chen W assisted with and was responsible for the reanalysis and reinterpretation of the data, figure preparation, comprehensive literature review, and the preparation and submission of the current manuscript version, with a new focus on the in vitro mechanisms of ABCB4 variants. Yang YF designed, and oversaw the entire project process. He reviewed the literature, revised the early versions of the manuscript, with a primary emphasis on the clinical characteristics of ABCB4 carriers and the analysis of clinical pathogenicity. The collaboration between Chen W and Yang YF was crucial for the publication of this manuscript.
Supported by the National Natural Science Foundation of China, No. 81970454.
Institutional review board statement: The study was reviewed and approved by The Second Hospital of Nanjing, The Affiliated to Nanjing University of Chinese Medicine, Institutional Review Board (Approval No.2021-LY-kt052).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All the data can be found in manuscript or Supplementary material.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong-Feng Yang, PhD, Chief Physician, Professor, Department of Hepatology, The Second Hospital of Nanjing, The Affiliated to Nanjing University of Chinese Medicine, The Affiliated to Southeast University Medical School, No. 1 Zhongfu Road, Gulou District, Nanjing 210003, Jiangsu Province, China. yangyongfeng@njucm.edu.cn
Received: January 8, 2025
Revised: February 26, 2025
Accepted: March 21, 2025
Published online: April 14, 2025
Processing time: 93 Days and 17.7 Hours
Core Tip

Core Tip: In this study, we included patients with cholestatic liver disease, and through whole exome sequencing, we identified five patients carrying ATP-binding cassette subfamily B member 4 variants. We analyzed their clinical, pathological, and prognosis. Compound heterozygosity leads to poor prognosis. We predicted the pathogenicity of the seven variants using bioinformatics tools and further investigated the pathogenicity of missense variants in vitro. We studied the mRNA, protein content, subcellular localization, and phosphatidylcholine secretion of the variants in vitro cell models. Ultimately, we found that all missense variants were pathogenic in clinical settings and in vitro.