Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy

Circ J. 2012;76(2):453-61. doi: 10.1253/circj.cj-11-0876. Epub 2011 Nov 23.


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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Adult
  • Aged
  • Asian People / genetics*
  • Asian People / statistics & numerical data*
  • Cardiac Myosins / genetics
  • Cardiomyopathy, Hypertrophic, Familial / ethnology*
  • Cardiomyopathy, Hypertrophic, Familial / genetics*
  • Carrier Proteins / genetics
  • Female
  • Geography
  • Humans
  • Japan / epidemiology
  • MAP Kinase Kinase Kinases / genetics
  • Male
  • Middle Aged
  • Myosin Heavy Chains / genetics
  • Myosin Light Chains / genetics
  • Pedigree
  • Prevalence
  • Protein Serine-Threonine Kinases
  • Sarcomeres / genetics*
  • Tropomyosin / genetics
  • Troponin T / genetics
  • Young Adult


  • ACTC1 protein, human
  • Actins
  • Carrier Proteins
  • MYH7 protein, human
  • Myosin Light Chains
  • TNNT2 protein, human
  • TPM1 protein, human
  • Tropomyosin
  • Troponin T
  • myosin-binding protein C
  • Protein Serine-Threonine Kinases
  • TNNI3K protein, human
  • MAP Kinase Kinase Kinases
  • Cardiac Myosins
  • Myosin Heavy Chains