title: Detection of mutations in symptomatic patients with hypertrophic cardiomyopathy in Taiwan.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder associated with sudden death, heart failure, and stroke. The aim of the present study was to evaluate the prevalence and types of mutations in symptomatic patients with HCM in Taiwan.
  
  
  METHODS
  Thirty-eight HCM index patients (mean age 60±16 years) underwent systematic mutation screening of eight sarcomeric genes: β-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), troponin I (TNNI3), myosin ventricular regulatory light chain 2 (MYL2), myosin ventricular essential light chain 1 (MYL3), α-tropomyosin (TPM1), and cardiac α-actin (ACTC), using direct DNA sequencing. In silico programs predicted damaging amino acids. In the positive families, genotype-phenotype correlation studies were done.
  
  
  RESULTS
  Overall, 13 mutations were identified in 13 index patients (34.2%). The three most frequently mutated genes were MYH7, MYBPC3, and TNNT2. One patient carried double mutations. Five mutations (MYH7 R147S; MYBPC3 R597Q; MYBPC3 W1007R; TNNI3 E124Q; MYL3 R63C) were novel; all were missense mutations. Analysis using in silico tools showed near consensus to classify these five novel mutations as pathological. Family pedigree analysis showed the presence of cosegregation in at least two affected members in each proband family, but incomplete penetrance in young family members with a positive genotype.
  
  
  CONCLUSIONS
  We identified 13 HCM pedigrees, including 5 carrying novel mutations and 1 with a double mutation. The three most commonly mutated genes were MYH7, MYBPC3, and TNNT2. These results, together with genetic counseling, could lead to earlier diagnosis and better management of family members at risk of HCM.
authors.affiliation: Division of Cardiology, Department of Medicine, Kaohsiung Veterans General Hospital, Taipei, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: krchiou@hotmail.com.
authors.forename: Kuan-Rau
authors.initials: KR
authors.lastname: Chiou
authors.affiliation: Division of cardiology, Yuansheng Hospital, Changhua, Taiwan, ROC.
authors.forename: Chien-Tung
authors.initials: CT
authors.lastname: Chu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: mjcharng@vghtpe.gov.tw.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Charng
mesh_terms: D000328:Adult; D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics; D010375:Pedigree; D017422:Sequence Analysis, DNA; D013624:Taiwan; D020107:Troponin T / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human; C545568:TNNT2 protein, human
keywords: Chinese; Genetics; Hypertrophic cardiomyopathy; Mutation; Taiwanese