Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers

Background— Mutations in LMNA ( lamin A/C ), which encodes lamin A and C, typically cause age-dependent cardiac phenotypes, including dilated cardiomyopathy, cardiac conduction disturbance, atrial fibrillation, and malignant ventricular arrhythmias. Although the type of LMNA mutations have been reported to be associated with susceptibility to malignant ventricular arrhythmias, the gene-based risk stratification for cardiac complications remains unexplored. Methods and Results— The multicenter cohort included 77 LMNA mutation carriers from 45 families; cardiac disorders were retrospectively analyzed. The mean age of patients when they underwent genetic testing was 45±17, and they were followed for a median 49 months. Of the 77 carriers, 71 (92%) were phenotypically affected and showed cardiac conduction disturbance (81%), low left ventricular ejection fraction ( Conclusions— The truncation mutations were associated with manifestation of cardiac phenotypes in LMNA -related cardiomyopathy, suggesting that genetic analysis might be useful for diagnosis and risk stratification.