title: The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.
abstract: OBJECTIVE
  The aim of the study was to screen 36 unrelated patients with hypertrophic cardiomyopathy (HCM; 16 familial and 20 sporadic cases) from a genetically homogeneous area in eastern Finland for variants in the cardiac beta-myosin heavy chain (beta-MHC) and alpha-tropomyosin (alpha-TM) genes.
  
  
  BACKGROUND
  Mutations in the beta-MHC and alpha-TM genes have been reported to be responsible for 30% to 40% and less than 5% of familial HCM cases, respectively. However, most genetic studies have included patients from tertiary care centers and are subject to referral bias.
  
  
  METHODS
  Exons 3-26 and 40 of the beta-MHC gene and the nine exons of the alpha-TM gene were screened with the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method. Linkage analyses between familial HCM locus and two intragenic polymorphic markers (MYO I and MYO II) of the beta-MHC gene were performed in 16 familial HCM kindreds.
  
  
  RESULTS
  A previously reported Arg719Trp (arginine converted to tryptophan in codon 719) mutation of the beta-MHC gene was found in one proband and two relatives. In addition, a novel Asn696Ser (asparagine converted to serine in codon 696) substitution was found in one HCM patient. No linkage between familial HCM and the beta-MHC gene was observed in 16 familial kindreds. A previously reported Aspl75Asn (aspartic acid converted to asparagine in codon 175) mutation of the alpha-TM gene was found in four probands and 16 relatives. Mutations in the beta-MHC and alpha-TM genes accounted for 6% and 25% familial HCM cases and 3% and 11% of all cases, respectively.
  
  
  CONCLUSIONS
  Our results indicate that the beta-MHC gene is not the predominant gene for HCM in the Finnish population, whereas HCM caused by the Aspl75Asn mutation of the a-TM gene is more common than previously reported.
authors.affiliation: Department of Medicine, University of Kuopio, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Jääskeläinen
authors.forename: M
authors.initials: M
authors.lastname: Soranta
authors.forename: R
authors.initials: R
authors.lastname: Miettinen
authors.forename: L
authors.initials: L
authors.lastname: Saarinen
authors.forename: J
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: K
authors.initials: K
authors.lastname: Silvennoinen
authors.forename: T
authors.initials: T
authors.lastname: Tikanoja
authors.forename: M
authors.initials: M
authors.lastname: Laakso
authors.forename: J
authors.initials: J
authors.lastname: Kuusisto
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005260:Female; D005387:Finland; D008040:Genetic Linkage / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D009206:Myocardium / Q000201:enzymology*; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D014335:Tropomyosin / Q000235:genetics
chemical_list: D014335:Tropomyosin; D018995:Myosin Heavy Chains