High incidence of sudden cardiac death with conduction disturbances and atrial cardiomyopathy caused by a nonsense mutation in the STA gene

摘要

BACKGROUND: The STA gene encodes emerin and is one of the genes that is affected in Emery-Dreifuss muscular dystrophy (EDMD). Although it has been reported that EDMD caused by STA gene mutation is associated with X-linked recessive inheritance, the genotype-phenotype correlations, with special reference to cardiac manifestations, are not well defined. METHODS AND RESULTS: We identified 16 carriers (7 males and 9 females) with a nonsense mutation in exon 6 of the STA gene in two EDMD families. Pacemakers were required for treatment of bradyarrhythmias in all 7 male carriers and in 2 of the 9 female carriers. In addition, 2 of the 9 female carriers displayed atrial fibrillation. In these 2 families, 3 males without pacemaker implantation, who were not tested genetically, had died suddenly. In these family members, the majority of carriers with the mutation had not been clinically diagnosed as having EDMD prior to genetic testing because of extremely mild or non-existent skeletal myopathy. CONCLUSIONS: EDMD caused by this mutation is characterized by atypical clinical features and incomplete penetrance of the clinical phenotype, and may result in serious cardiac complications including sudden death. Approaches to preventing possible sudden death in carriers with the STA gene mutation require further study.