title: 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 beta-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), and alpha-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.
authors.affiliation: Department of Cardiac and Thoracic Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D-13353, Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Daehmlow
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Tanja
authors.initials: T
authors.lastname: Knueppel
authors.forename: Christoph
authors.initials: C
authors.lastname: Gille
authors.forename: Cornelius
authors.initials: C
authors.lastname: Froemmel
authors.forename: Manfred
authors.initials: M
authors.lastname: Hummel
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012518:Sarcomeres; D014335:Tropomyosin / Q000235:genetics; D020107:Troponin T / Q000235:genetics; D024723:Ventricular Myosins / Q000737:chemistry / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D009124:Muscle Proteins; D014335:Tropomyosin; D020107:Troponin T; D024723:Ventricular Myosins; D000099163:Myosin Binding Protein C