Affiliation: | aSamsung Biomedical Research Institute, Seoul, South Korea bDepartment of Tissue Physiology, Division of Adult Diseases, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan cCardiology Division, Samsung Medical Center, College of Medicine, Sung Kyun Kwan University, Seoul, South Korea dDepartment of Internal Medicine, University of Inje, Seoul Paik Hospital, Seoul, South Korea |
Abstract: | The clinical course and prognosis of familial hypertrophic cardiomyopathy (HCM) are different according to the type of mutation in the genes for sarcomere proteins. It has been disputed that a mutation, which occurs at a functionally important region in the sarcomere proteins, may increase the penetrance and expressivity of the disease. We searched for a causative mutation in an HCM family, which is characterized by early expression of clinical phenotype, high incidence of sudden death at young ages, and progressive heart 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 progressive heart failure or poor left ventricular systolic functions. PCR-SSCP (polymerase chain reaction–single strand confirmation polymorphism) analysis of genomic DNAs isolated from peripheral blood leukocytes of the family members identified a Gly716Arg mutation in the cardiac β-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, which occurs at a functionally important site of the myosin heavy chain, is associated with the high penetrance and early expression of HCM. |