1. ¹Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark
2. ²Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark
3. ³Department of Biomedical Sciences, MRC/US Centre for Molecular and Cellular Biology, University of Stellenbosch Health Sciences Faculty, Tygerberg, South Africa

Correspondence: Dr DV Møller, Department of Cardiology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen O, Denmark. Tel: +45 35458619; Fax: +45 35452549; E-mail: dvega@gmx.net

Received 10 October 2008; Revised 29 January 2009; Accepted 5 February 2009; Published online 18 March 2009.

Abstract

We investigated a Danish cohort of 31 unrelated patients with idiopathic dilated cardiomyopathy (IDC), to assess the role that mutations in sarcomere protein genes play in IDC. Patients were genetically screened by capillary electrophoresis single strand conformation polymorphism and subsequently by bidirectional DNA sequencing of conformers in the coding regions of MYH7, MYBPC3, TPM1, ACTC, MYL2, MYL3, TNNT2, CSRP3 and TNNI3. Eight probands carried disease-associated genetic variants (26%). In MYH7, three novel mutations were found; in MYBPC3, one novel variant and two known mutations were found; and in TNNT2, a known mutation was found. One proband was double heterozygous. We find evidence of phenotypic plasticity: three mutations described earlier as HCM causing were found in four cases of IDC, with no history of a hypertrophic phase. Furthermore, one pedigree presented with several cases of classic DCM as well as one case with left ventricular non-compaction. Disease-causing sarcomere gene mutations were found in about one-quarter of IDC patients, and seem to play an important role in the causation of the disease. The genetics is as complex as seen in HCM. Thus, our data suggest that a genetic work-up should include screening of the most prominent sarcomere genes even in the absence of a family history of the disease.