Characterization of a Unique Form of Arrhythmic Cardiomyopathy Caused by Recessive Mutation in LEMD2

Abstract

Nuclear envelope proteins have been shown to play an important role in the pathogenesis of inherited dilated cardiomyopathy. Here, we present a remarkable cardiac phenotype caused by a homozygous <i>LEMD2</i> mutation in patients of the Hutterite population with juvenile cataract. Mutation carriers develop arrhythmic cardiomyopathy with mild impairment of left ventricular systolic function but severe ventricular arrhythmias leading to sudden cardiac death. Affected cardiac tissue from a deceased patient and fibroblasts exhibit elongated nuclei with abnormal condensed heterochromatin at the periphery. The patient fibroblasts demonstrate cellular senescence and reduced proliferation capacity, which may suggest an involvement of LEM domain containing protein 2 in chromatin remodeling processes and premature aging.