Functional characterization of ABCC8 variants of unknown significance based on bioinformatics predictions, splicing assays, and protein analyses: Benefits for the accurate diagnosis of congenital hyperinsulinism.

ABSTRACT: ABCC8 encodes the SUR1 subunit of the β-cell ATP-sensitive potassium channel whose loss of function causes congenital hyperinsulinism (CHI). Molecular diagnosis is critical for optimal management of CHI patients. Unfortunately, assessing the impact of ABCC8 variants on RNA splicing remains very challenging as this gene is poorly expressed in leukocytes. Here, we performed bioinformatics analysis and cell-based minigene assays to assess the impact on splicing of 13 ABCC8 variants identified in 20 CHI patients. Next, channel properties of SUR1 proteins expected to originate from minigene-detected in-frame splicing defects were analyzed after ectopic expression in COSm6 cells. Out of the analyzed variants, seven induced out-of-frame splicing defects and were therefore classified as recessive

SUBMITTER: Saint-Martin C 

PROVIDER: S-EPMC8049974 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature