MUTATIONS IN THE CARDIAC TROPONIN-I GENE ASSOCIATED WITH HYPERTROPHICCARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden dea th in the young, is an autosomal dominant disease characterized by ven tricular hypertrophy accompanied by myofibrillar disarrays(1). Linkage studies and candidate-gene approaches have demonstrated that about ha lf of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC)(2,3), cardiac troponin T (cTnT)( 4,5), alpha-tropomyosin (alpha TM)(5,6), cardiac myosin binding protei n C (cMBP-C)(7-9), ventricular myosin essential light chain (vMLC1)(10 ) and ventricular myosin regulatory light chain (vMLC2)(10) genes. Oth er disease genes remain unknown. Because all the known disease genes e ncode major contractile elements in cardiac muscle(11), we have system atically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC)( 12) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients(13).