Evaluation in Monogenic Diabetes of the Impact of <i>GCK</i>, <i>HNF1A</i>, and <i>HNF4A</i> Variants on Splicing through the Combined Use of In Silico Tools and Minigene Assays.

ABSTRACT: Variants in GCK, HNF1A, and HNF4A genes are the three main causes of monogenic diabetes. Determining the molecular etiology is essential for patients with monogenic diabetes to benefit from the most appropriate treatment. The increasing number of variants of unknown significance (VUS) is a major issue in genetic diagnosis, and assessing the impact of variants on RNA splicing is challenging, particularly for genes expressed in tissues not easily accessible as in monogenic diabetes. The in vitro functional splicing assay based on a minigene construct is an appropriate approach. Here, we performed in silico analysis using SpliceAI and SPiP and prioritized 36 spliceogenic variants in GCK, HNF1A, and HNF4A. Predictions were secondarily compared with Pan

SUBMITTER: Bouvet D 

PROVIDER: S-EPMC11919142 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature