title: Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland.
  
  
  OBJECTIVE
  To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland. Patients and methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in 306 unrelated Finnish patients with HCM from the regions covering a population of ∼4,000,000.
  
  
  RESULTS
  The TPM1-D175N mutation was found in 20 patients (6.5%) and the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations showed regional clustering. TPM1-D175N was prevalent in central and western Finland, and MYBPC3-Q1061X in central and eastern Finland.
  
  
  CONCLUSIONS
  The TPM1-D175N and MYBPC3-Q1061X mutations account for a substantial part of all HCM cases in the Finnish population, indicating that routine genetic screening of these mutations is warranted in Finnish patients with HCM.
authors.affiliation: Heart Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Pertti
authors.initials: P
authors.lastname: Jääskeläinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Heliö
authors.forename: Katriina
authors.initials: K
authors.lastname: Aalto-Setälä
authors.forename: Maija
authors.initials: M
authors.lastname: Kaartinen
authors.forename: Erkki
authors.initials: E
authors.lastname: Ilveskoski
authors.forename: Liisa
authors.initials: L
authors.lastname: Hämäläinen
authors.forename: John
authors.initials: J
authors.lastname: Melin
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Helena
authors.initials: H
authors.lastname: Kervinen
authors.forename: Juha
authors.initials: J
authors.lastname: Mustonen
authors.forename: Jukka
authors.initials: J
authors.lastname: Juvonen
authors.forename: Mari
authors.initials: M
authors.lastname: Niemi
authors.forename: Paavo
authors.initials: P
authors.lastname: Uusimaa
authors.forename: Matti
authors.initials: M
authors.lastname: Huttunen
authors.forename: Matti
authors.initials: M
authors.lastname: Kotila
authors.forename: Mikko
authors.initials: M
authors.lastname: Pietilä
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005387:Finland; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014335:Tropomyosin / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D014335:Tropomyosin; D000099163:Myosin Binding Protein C