ACTIN MUTATIONS IN DILATED CARDIOMYOPATHY, A HERITABLE FORM OF HEART-FAILURE

To test the hypothesis that actin dysfunction leads to heart failure, patients with hereditary idiopathic dilated cardiomyopathy (IDC) were examined for mutations in the cardiac actin gene (ACTC). Missense muta tions in ACTC that cosegregate with IDC were identified in two unrelat ed families. Both mutations affect universally conserved amino acids i n domains of actin that attach to Z bands and intercalated discs. Coup led with previous data showing that dystrophin mutations also cause di lated cardiomyopathy, these results raise the possibility that defecti ve transmission of force in cardiac myocytes is a mechanism underlying heart failure.