Two novel mutations in the β-myosin heavy chain gene associated with dilated cardiomyopathy

Background: Dilated cardiomopathy (DCM) is familial in approximately 20-35% of cases of idiopathic DCM. Several mutations in the different sarcomere protein genes have been reported to cause DCM. Aims: We wanted to investigate the role of sarcomere protein gene variants in Finnish DCM patients. Methods and results: We screened all coding exons of five sarcomere protein genes (beta-myosin heavy chain, alpha-tropomyosin, troponin C, troponin I and troponin T) in a well-characterized population of 52 DCM patients in Eastern Finland by the PCR-SSCP and sequencing method. Two novel mutations, Arg1053Gln and Arg1500Trp, in the beta-myosin heavy chain gene in two index patients were detected. The proband with the Argl053Gln mutation had a dilated left ventricle and impaired systolic function, but other family members carrying this mutation presented with septal hypertrophy. It thus seems that the Argl053Gln mutation is primarily a HCM mutation, which can also lead to DCM. The other mutation, Argl500Trp, was associated with a typical DCM phenotype. The Argl500Trp mutation carrier had only one family member alive, but she did not carry the mutation and, therefore, cosegregation of the mutation and the disease in this family could not be reliably verified. No disease-causing mutations were found in the other sarcomere protein genes. Conclusions: Two novel mutations in the beta-myosin heavy chain gene were detected in patients with DCM. Overall, mutations in the Pmyosin heavy chain gene seem to be relatively uncommon in Finnish DCM patients. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.