Presence of Hypertrophic Cardiomyopathy Related Gene Mutations and Clinical Manifestations in Vietnamese Patients With Hypertrophic Cardiomyopathy

Circ J. 2019 Aug 23;83(9):1908-1916. doi: 10.1253/circj.CJ-19-0190. Epub 2019 Jul 12.

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is associated primarily with pathogenic mutations in sarcomeric genes. The aim of this study was to identify the prevalence and distribution of disease-causing mutations in HCM-associated genes and the genotype-phenotype relationship in Vietnamese patients with HCM.

Methods and results: Genetic testing was performed by next-generation sequencing in 104 unrelated probands for 23 HCM-related genes and in 57 family members for the mutation(s) detected. Clinical manifestations were recorded for genotype-phenotype correlation analysis. Mutation detection rate was 43.4%. Mutations inMYBPC3accounted for 38.6%, followed byTPM1(20.5%),MYH7(18.2%),TNNT2(9.1%),TNNI3(4.5%) andMYL2(2.3%). A mutation inGLAassociated with Fabry disease was found in 1 patient. A mutation inTPM1(c.842T>C, p.Met281Thr) was identified in 8 unrelated probands (18.2%) and 8 family members from 5 probands. Genotype-positive status related toMYH7,TPM1, andTNNT2mutations was associated with severe clinical manifestations.MYH7-positive patients displayed worse prognosis compared withMYBPC3-positive patients. Interestingly,TPM1c.842T>C mutation was associated with high penetrance and severe HCM phenotype.

Conclusions: We report for the first time the prevalence of HCM-related gene variants in Vietnamese patients with HCM.MYH7,TPM1, andTNNT2mutations were associated with unfavorable prognosis.

Keywords: Genetic mutations; Hypertrophic cardiomyopathy; Next-generation sequencing.

MeSH terms

  • Adult
  • Cardiac Myosins / genetics*
  • Cardiomyopathy, Hypertrophic / diagnosis
  • Cardiomyopathy, Hypertrophic / epidemiology
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / physiopathology
  • DNA Mutational Analysis
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mutation Rate
  • Mutation*
  • Myosin Heavy Chains / genetics*
  • Penetrance
  • Phenotype
  • Prevalence
  • Prognosis
  • Risk Factors
  • Sarcomeres / genetics*
  • Severity of Illness Index
  • Tropomyosin / genetics*
  • Troponin T / genetics*
  • Vietnam / epidemiology

Substances

  • MYH7 protein, human
  • TNNT2 protein, human
  • TPM1 protein, human
  • Tropomyosin
  • Troponin T
  • Cardiac Myosins
  • Myosin Heavy Chains