Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1.

ABSTRACT:

Background

Left ventricular noncompaction (LVNC) is a prevalent cardiomyopathy associated with excessive trabeculation and thin compact myocardium. Patients with LVNC are vulnerable to cardiac dysfunction and at high risk of sudden death. Although sporadic and inherited mutations in cardiac genes are implicated in LVNC, understanding of the mechanisms responsible for human LVNC is limited.

Methods

We screened the complete exome sequence database of the Pediatrics Cardiac Genomics Consortium and identified a cohort with a de novo CHD4 (chromodomain helicase DNA-binding protein 4) proband, CHD4^M202I, with congenital heart defects. We engineered a humanized mouse model of CHD4^M202I (mouse CHD4^M195I). Histological analysis, immunohistochemistry,

SUBMITTER: Shi W 

PROVIDER: S-EPMC10284140 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature