Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy: a comprehensive outpatient perspective

J Am Coll Cardiol. 2002 Jun 19;39(12):2042-8. doi: 10.1016/s0735-1097(02)01900-9.


Objectives: The goal of this study was to determine the prevalence of "malignant" mutations in hypertrophic cardiomyopathy (HCM).

Background: Previous genotype-phenotype studies have implicated four mutations (R403Q, R453C, G716R and R719W) as highly malignant defects in the beta-myosin heavy chain (MYH7). In the cardiac troponin T gene (TNNT2), a specific mutation (R92W) has been associated with high risk of sudden death. Routine clinical screening for these malignant mutations has been suggested to identify high-risk individuals.

Methods: We screened 293 unrelated individuals with HCM seen at the Mayo Clinic in Rochester, Minnesota, between April 1997 and October 2000. Deoxyribonucleic acid (DNA) was obtained after informed consent; amplification of MYH7 exons 13 (R403Q), 14 (R453C) and 19 (G716R and R719W), and TNNT2 exon 9 (R92W) was performed by polymerase chain reaction. The mutations were detected using denaturing high-performance liquid chromatography and automated DNA sequencing.

Results: The mean age at diagnosis was 42 years with 53 patients diagnosed before age 25. The mean maximal left ventricular wall thickness was 21 mm. Nearly one-third of cases were familial and one-fourth had a family history of sudden cardiac death. Only 3 of the 293 patients possessed one of the five "malignant" mutations, and all 3 patients were <25 years of age at presentation (p < 0.006).

Conclusions: This finding underscores the profound genetic heterogeneity in HCM. Only 1% of unrelated individuals seen at a tertiary referral center for HCM possessed one of the five "malignant" mutations that were examined. Routine clinical testing for these specific mutations is of low yield.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiomyopathy, Hypertrophic / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation
  • Myosin Heavy Chains / genetics*
  • Ventricular Myosins / genetics*


  • Ventricular Myosins
  • Myosin Heavy Chains