Worse prognosis with gene mutations of beta-myosin heavy chain than myosin-binding protein C in Chinese patients with hypertrophic cardiomyopathy

Clin Cardiol. 2008 Mar;31(3):114-8. doi: 10.1002/clc.20151.

Abstract

Background: No data are available on survival analysis and longitudinal evolution of patients with gene mutations of beta-myosin heavy chain (MYH7) and myosin binding protein C (MYBPC3) in Chinese.

Hypothesis: To prospectively investigate whether different gene mutations confer distinct prognosis.

Methods: We performed a prospective study in 70 HCM patients and 46 genetically affected family members without HCM-phenotype with direct DNA sequencing of MYH7 and MYBPC3, clinical assessments, and 5.8 +/- 1.8 years follow-up.

Results: After follow-up, more surgical intervention (8/52 versus 0/18, p < 0.001), higher sudden death risk (7/52 versus 0/18, p < 0.001) and shorter life span were found in patients with MYH7 mutations than in patients with MYBPC3 mutations (45.1 +/- 14.0 versus 73.5 +/- 7.5 years, p = 0.03). Seven of the 27 mutation carriers of MYH7 had clinical presentations of HCM, but no carriers of MYBPC3 mutations developed to HCM during follow-up. Maximal wall thickness was thicker in the patients carrying mutations in the global region of MYH7 than in those carrying mutations in the rod region of MYH7 (21.5 +/- 6.6 versus 15 +/- 6.1 mm, p < 0.05) at baseline. More sudden death (7/41 versus 0/11) and left ventricular dysfunction (NYHA Class III approximately IV, 17/32 versus 1/10) were identified in patients with mutations in the global region of MYH7 than in patients with other mutations.

Conclusions: MYH7 mutations, especially in the global region, cause malignant clinical phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Cardiomyopathy, Hypertrophic / epidemiology
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / mortality
  • Carrier Proteins / genetics*
  • China / epidemiology
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Myosin Heavy Chains / genetics*
  • Phenotype
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Ventricular Myosins / genetics*

Substances

  • Carrier Proteins
  • myosin-binding protein C
  • Ventricular Myosins
  • Myosin Heavy Chains