Modeling <i>SMAD2</i> Mutations in Induced Pluripotent Stem Cells Provides Insights Into Cardiovascular Disease Pathogenesis.

ABSTRACT:

Background

SMAD2 is a coregulator that binds a variety of transcription factors in human development. Heterozygous SMAD2 loss-of-function and missense variants are identified in patients with congenital heart disease (CHD) or arterial aneurysms. Mechanisms that cause distinct cardiovascular phenotypes remain unknown. We aimed to define transcriptional and epigenetic effects of SMAD2 variants and their role in CHD. We also assessed the function of SMAD2 missense variants of uncertain significance.

Methods and results

Rare SMAD2 variants (minor allele frequency ≤10^-5) were identified in exome sequencing of 11 336 participants with CHD. We constructed isogenic induced pluripotent stem cells with heterozygous or homozygous loss-of-function

SUBMITTER: Ward T 

PROVIDER: S-EPMC12184555 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature