World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(14)

Published: April 9, 2025

ATP-binding cassette subfamily B member 4 (ABCB4) deficiency is associated with cholestatic liver disease primarily because of missense mutations, and many variants remain unidentified. Here, we validate the pathogenicity mechanism ABCB4 in clinical vitro trials, hypothesizing that these are responsible for impaired biliary function contribute to development diseases. To clarify functional features variants. Clinical data were collected from five patients was initially not detected by routine examinations. Later, whole-exome sequencing confirmed treated January 2017 December 2023. Pathogenic mechanisms analyzed using bioinformatics tools, a cell model established investigate mRNA expression, multidrug resistance protein 3 (MDR3) cellular localization, phosphatidylcholine secretion. Results compared Student's t-tests. Five (c.1757T>A, c.1865G>A, c.2362C>T, c.2777C>T c.3250C>T), one intron variant (c.537-32G>T), synonymous (c.C504T) identified. Three had various degrees cholestasis, two presented cirrhosis, all elevated gamma-glutamyl transferase. four who underwent biopsy bile duct dilation, gallstones. Two normal reduced MDR3 immunohistochemical levels. Bioinformatic analysis indicated likely pathogenic except c.C504T variant. None influenced subcellular Localization vitro. However, c.1865G>A significantly decreased values, down-regulated This study uncovered new emphasized potential specific The findings provided insight into underlying ABCB4-related

Language: Английский