Prioritizing de novo potential non-canonical splicing variants in neurodevelopmental disorders.

ABSTRACT:

Background

Genomic variants outside of the canonical splicing site (±2) may generate abnormal mRNA splicing, which are defined as non-canonical splicing variants (NCSVs). However, the clinical interpretation of NCSVs in neurodevelopmental disorders (NDDs) is largely unknown.

Methods

We investigated the contribution of NCSVs to NDDs from 345,787 de novo variants (DNVs) in 47,574 patients with NDDs. We performed functional enrichment and protein-protein interaction analysis to assess the association between genes carrying prioritised NCSVs and NDDs. Minigene was used to validate the impact of NCSVs on mRNA splicing.

Findings

We observed significantly more NCSVs (p = 0.02, odds ratio [OR] = 2.05) among patients with NDD than in controls. Both canonical splicing variants

SUBMITTER: Li K 

PROVIDER: S-EPMC10767160 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature