Novel mutations in sarcomeric protein genes in dilated cardiomyopathy

Abstract

Mutations in sarcomeric protein genes have been reported to cause dilated cardiomyopathy (DCM). In order to detect novel mutations we screened the sarcomeric protein genes β-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), and α-tropomyosin (TPM1) in 46 young patients with DCM. Mutation screening was done using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The mutations in MYH7 were projected onto the protein data bank-structure (pdb) of myosin of striated muscle. In MYH7 two mutations (Ala223Thr and Ser642Leu) were found in two patients. Ser642Leu is part of the actin–myosin interface. Ala223Thr affects a buried residue near the ATP binding site. In MYBPC3 we found one missense mutation (Asn948Thr) in a male patient. None of the mutations were found in 88 healthy controls and in 136 patients with hypertrophic cardiomyopathy (HCM). Thus mutations in HCM causing genes are not rare in DCM and have potential for functional relevance.