Contribution of Previously Unrecognized RNA Splice-Altering Variants to Congenital Heart Disease.

ABSTRACT:

Background

Known genetic causes of congenital heart disease (CHD) explain <40% of CHD cases, and interpreting the clinical significance of variants with uncertain functional impact remains challenging. We aim to improve diagnostic classification of variants in patients with CHD by assessing the impact of noncanonical splice region variants on RNA splicing.

Methods

We tested de novo variants from trio studies of 2649 CHD probands and their parents, as well as rare (allele frequency, <2×10^-6) variants from 4472 CHD probands in the Pediatric Cardiac Genetics Consortium through a combined computational and in vitro approach.

Results

We identified 53 de novo and 74 rare variants in CHD cases that alter splicing and thus are loss of function. Of these,

SUBMITTER: Jang MY 

PROVIDER: S-EPMC10404383 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature