title: Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM), which is inherited as an autosomal dominant trait, is the most prevalent hereditary cardiac disease. Although there are several reports on the systematic screening of mutations in the disease-causing genes in European and American populations, only limited information is available for Asian populations, including Japanese.
  
  
  RESULTS
  Genetic screening of disease-associated mutations in 8 genes for sarcomeric proteins, MYH7, MYBPC3, MYL2, MYL3, TNNT2, TNNI3, TPM1, and ACTC, was performed by direct sequencing in 112 unrelated Japanese proband patients with familial HCM; 37 different mutations, including 13 novel ones in 5 genes, MYH7, MYBPC3, TNNT2, TNNI3, and TPM1, were identified in 49 (43.8%) patients. Among them, 3 carried compound heterozygous mutations in MYBPC3 or TNNT2. The frequency of patients carrying the MYBPC3, MYH7, and TNNT2 mutations were 19.6%, 10.7%, and 8.9%, respectively, and the most frequently affected genes in the northeastern and southwestern parts of Japan were MYBPC3 and MYH7, respectively. Several mutations were found in multiple unrelated proband patients, for which the geographic distribution suggested founder effects of the mutations.
  
  
  CONCLUSIONS
  This study demonstrated the frequency and distribution of mutations in a large cohort of familial HCM in Japan.
authors: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors: Haruna
authors: H
authors: Otsuka
authors: Takuro
authors: T
authors: Arimura
authors: Tadaaki
authors: T
authors: Abe
authors: Hiroya
authors: H
authors: Kawai
authors: Yoshiyasu
authors: Y
authors: Aizawa
authors: Toru
authors: T
authors: Kubo
authors: Hiroaki
authors: H
authors: Kitaoka
authors: Hiroshi
authors: H
authors: Nakamura
authors: Kazufumi
authors: K
authors: Nakamura
authors: Hiroshi
authors: H
authors: Okamoto
authors: Fukiko
authors: F
authors: Ichida
authors: Mamoru
authors: M
authors: Ayusawa
authors: Shinichi
authors: S
authors: Nunoda
authors: Mitsuaki
authors: M
authors: Isobe
authors: Masunori
authors: M
authors: Matsuzaki
authors: Yoshinori L
authors: YL
authors: Doi
authors: Keiichi
authors: K
authors: Fukuda
authors: Taishi
authors: T
authors: Sasaoka
authors: Toru
authors: T
authors: Izumi
authors: Naoto
authors: N
authors: Ashizawa
authors: Akinori
authors: A
authors: Kimura
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data*; D024722:Cardiac Myosins / Q000235:genetics; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000208:ethnology* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D005843:Geography; D006801:Humans; D007564:Japan / Q000453:epidemiology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000235:genetics; D018994:Myosin Light Chains / Q000235:genetics; D010375:Pedigree; D015995:Prevalence; D017346:Protein Serine-Threonine Kinases; D012518:Sarcomeres / Q000235:genetics*; D014335:Tropomyosin / Q000235:genetics; D020107:Troponin T / Q000235:genetics; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D000199:Actins; D024722:Cardiac Myosins; D002352:Carrier Proteins; D020930:MAP Kinase Kinase Kinases; D018995:Myosin Heavy Chains; D018994:Myosin Light Chains; D017346:Protein Serine-Threonine Kinases; D014335:Tropomyosin; D020107:Troponin T; D000099163:Myosin Binding Protein C; C526913:ACTC1 protein, human; C501641:MYH7 protein, human; C545568:TNNT2 protein, human; C490775:TPM1 protein, human; C481078:TNNI3K protein, human