Neonatal-lethal dilated cardiomyopathy due to a homozygous LMOD2 donor splice-site variant.

ABSTRACT: Dilated cardiomyopathy (DCM) is characterized by cardiac enlargement and impaired ventricular contractility leading to heart failure. A single report identified variants in leiomodin-2 (LMOD2) as a cause of neonatally-lethal DCM. Here, we describe two siblings with DCM who died shortly after birth due to heart failure. Exome sequencing identified a homozygous LMOD2 variant in both siblings, (GRCh38)chr7:g.123656237G > A; NM_207163.2:c.273 + 1G > A, ablating the donor 5' splice-site of intron-1. Pre-mRNA splicing studies and western blot analysis on cDNA derived from proband cardiac tissue, MyoD-transduced proband skin fibroblasts and HEK293 cells transfected with LMOD2 gene constructs established variant-associated absence of canonically spliced LMOD2 mRNA and full-length LMOD2 protein. Im

SUBMITTER: Yuen M 

PROVIDER: S-EPMC8989920 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature