title: Two novel mutations in the beta-myosin heavy chain gene associated with dilated cardiomyopathy.
abstract: BACKGROUND
  Dilated cardiomyopathy (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.
  
  
  OBJECTIVE
  We wanted to investigate the role of sarcomere protein gene variants in Finnish DCM patients.
  
  
  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 Arg1053Gln 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 Arg1053Gln mutation is primarily a HCM mutation, which can also lead to DCM. The other mutation, Arg1500Trp, was associated with a typical DCM phenotype. The Arg1500Trp 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 beta-myosin heavy chain gene seem to be relatively uncommon in Finnish DCM patients.
authors.affiliation: Department of Medicine, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Kärkkäinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Heliö
authors.forename: Pertti
authors.initials: P
authors.lastname: Jääskeläinen
authors.forename: Raija
authors.initials: R
authors.lastname: Miettinen
authors.forename: Petri
authors.initials: P
authors.lastname: Tuomainen
authors.forename: Kari
authors.initials: K
authors.lastname: Ylitalo
authors.forename: Maija
authors.initials: M
authors.lastname: Kaartinen
authors.forename: Eeva
authors.initials: E
authors.lastname: Reissell
authors.forename: Lauri
authors.initials: L
authors.lastname: Toivonen
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Keijo
authors.initials: K
authors.lastname: Peuhkurinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001120:Arginine; D001794:Blood Pressure / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005973:Glutamine; D006333:Heart Failure / Q000235:genetics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012518:Sarcomeres / Q000235:genetics*; D013318:Stroke Volume / Q000235:genetics; D014335:Tropomyosin / Q000235:genetics; D019209:Troponin C / Q000235:genetics; D019210:Troponin I / Q000235:genetics; D020107:Troponin T / Q000235:genetics; D014364:Tryptophan; D024723:Ventricular Myosins / Q000235:genetics*
chemical_list: D014335:Tropomyosin; D019209:Troponin C; D019210:Troponin I; D020107:Troponin T; D005973:Glutamine; D014364:Tryptophan; D001120:Arginine; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains