Early expression of a malignant phenotype of familial hypertrophic Cardiomyopathy associated with a Gly716Arg myosin heavy chain mutation in Korean family

The clinical course and prognosis of familial hypertrophic cardiomyopathy ( HCM) are different according to the type of mutation in the genes for sarco mere proteins. It has been disputed that a mutation, which occurs at a func tionally important region in the sarcomere proteins, may increase the penet rance and expressivity of the disease. We searched for a causative mutation in an HCM family, which is characterized by early expression of clinical p henotype, high incidence of sudden death at young ages, and progressive hea rt failure in adults. Among the 32 family members in 4 generations, 13 were affected; 4 died suddenly before age 16, 2 children have already had full expression of the cardiac hypertrophy, and other adults have either progres sive heart failure or poor left ventricular systolic functions. PCR-SSCP (p olymerase chain reaction-single strand confirmation polymorphism) analysis of genomic DNAs isolated from peripheral blood leukocytes of the family mem bers identified a Gly716Arg mutation in the cardiac beta-myosin heavy chain gene, which was cosegregated with the clinical phenotype. The mutation is localized near a functionally important site of the myosin heavy chain, the 2 active thiols, which contribute to the adenosine triphosphatase activity of myosin S1. This family provides further evidence that the mutation, whi ch occurs at a functionally important site of the myosin heavy chain, is as sociated with the high penetrance and early expression of HCM. (C) 1998 by Excerpta Medica, Inc.