A recurrent ABCC2 c.2439 + 5G > A variant disturbs mRNA splicing and causes Dubin-Johnson syndrome.

ABSTRACT:

Background

Hyperbilirubinemia is the main clinical manifestation of Dubin-Johnson syndrome (DJS), of which most cases can be attributed to the variants in the ABCC2 gene. This study aimed to characterize the mechanism of a splicing variant of the ABCC2 gene and interrogate the variant pathogenicity.

Methods

Whole exome sequencing (WES) was performed to identify potential genetic causes. Bioinformatics analysis was performed to predict the variant pathogenicity. Minigene assays were performed to investigate the effects of the identified variant on mRNA splicing. Western blot (WB) experiments were performed to verify the impact of the variant on protein expression. Protein subcellular localization was analyzed by indirect immunofluorescence (IF).

Results

Genetic analysi

SUBMITTER: Sun R 

PROVIDER: S-EPMC12275409 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature