Detection of mutations in symptomatic patients with hypertrophic cardiomyopathy in Taiwan

Kuan Rau Chiou, Chien Tung Chu, Min Ji Charng

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)250-256
Number of pages7
JournalJournal of Cardiology
Volume65
Issue number3
DOIs
Publication statusPublished - Mar 1 2015
Externally publishedYes

Fingerprint

Hypertrophic Cardiomyopathy
Taiwan
Mutation
Myosin Light Chains
Pedigree
Computer Simulation
Genes
Tropomyosin
Troponin T
Inborn Genetic Diseases
Troponin I
Myosin Heavy Chains
Penetrance
Genetic Counseling
Genetic Association Studies
Missense Mutation
Sudden Death
DNA Sequence Analysis
Actins
Early Diagnosis

Keywords

  • Chinese
  • Genetics
  • Hypertrophic cardiomyopathy
  • Mutation
  • Taiwanese

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Detection of mutations in symptomatic patients with hypertrophic cardiomyopathy in Taiwan. / Chiou, Kuan Rau; Chu, Chien Tung; Charng, Min Ji.

In: Journal of Cardiology, Vol. 65, No. 3, 01.03.2015, p. 250-256.

Research output: Contribution to journalArticle

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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.",
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N2 - 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.

AB - 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.

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