Clinical, immunohistochemical, and genetic characterization of splice-altering biallelic DES variants: Therapeutic implications.

ABSTRACT: Pathogenic variants in the DES gene clinically manifest as progressive skeletal muscle weakness, cardiomyopathy with associated severe arrhythmias, and respiratory insufficiency, and are collectively known as desminopathies. While most DES pathogenic variants act via a dominant mechanism, recessively acting variants have also been reported. Currently, there are no effective therapeutic interventions for desminopathies of any type. Here, we report an affected individual with rapidly progressive dilated cardiomyopathy, requiring heart transplantation at age 13 years, in the setting of childhood-onset skeletal muscle weakness. We identified biallelic DES variants (c.640-13 T>A and c.1288+1 G>A) and show aberrant DES gene splicing in the affected individual's muscle. Through the generation of

SUBMITTER: Geist Hauserman J 

PROVIDER: S-EPMC10876619 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature