DNA methylation analysis of NOTCH1 variants reveals the first episignature for non-syndromic congenital heart defects.

ABSTRACT:

Background

Congenital heart defects (CHDs) are the most common malformation amongst newborns, with a prevalence of approximately 0.8-2%. The etiology of CHD is highly complex and can be linked to genetic and nongenetic factors. The molecular basis remains partially unclear, and only a minority of patients can be assigned to clear monogenic causes.

Methods

Here we analyzed a cohort of 3907 CHD cases and population-matched controls using exome sequencing. In addition, we employed epigenetic profiling on a subset of cases that harbored rare NOTCH1 variants.

Results

We identified 24 pathogenic or likely pathogenic single nucleotide variants (SNVs) in NOTCH1 in our exome cohort, as well as a further 15 variants of uncertain significance (VUS) likely to have a deleterious e

SUBMITTER: Dombrowsky G 

PROVIDER: S-EPMC12781588 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature