Molecular basis of hypertrophic and dilated cardiomyopathy

Tex Heart Inst J. 1994;21(1):6-15.

Abstract

Hypertrophic cardiomyopathy is a heterogeneous disease with autosomal dominant Mendelian inheritance. In 1989, the 1st locus for hypertrophic cardiomyopathy was mapped to cardiac myosin genes located on chromosome 14q1. Soon, several mutations that cosegregated with inheritance of the disease were identified in the beta-myosin heavy chain gene, or MHY7. More than 30 missense mutations and 1 deletion mutation in the beta-myosin heavy chain gene have since been described. Recently, expression of both the mutant beta-myosin heavy chain mRNA and the mutant protein has been shown in the cardiac and skeletal muscles of individuals with hypertrophic cardiomyopathy. Characterization of the clinical features of beta-myosin heavy chain mutations has shown that certain mutations, such as Arg403Gln and Arg719Trp mutations, are associated with high rate of sudden cardiac death. In addition to the beta-myosin heavy chain gene, 3 new loci for hypertrophic cardiomyopathy have recently been described, but the candidate genes have not yet been identified. Dilated cardiomyopathy can be inherited as an autosomal dominant, autosomal recessive, and X-linked disease. The familial form of dilated cardiomyopathy comprises approximately 20% of the cases of idiopathic cardiomyopathy. Echocardiographic abnormalities such as left ventricular enlargement are present in 10% of asymptomatic relatives. No gene for familial dilated cardiomyopathy has been identified, but linkage studies using polymorphic, short-tandem repeat markers are ongoing. Dilated cardiomyopathy is a common manifestation of Duchenne/Becker muscular dystrophy. Heart failure is a common cause of death in the affected individuals. The gene responsible for this disease is the dystrophin gene located on X chromosome. There have been reports in these patients of several dystrophin-gene deletion mutations, which result in a decrease in the expression of the dystrophin protein in the cardiac and skeletal tissues. X-linked cardiomyopathy, in which the disease is restricted to the heart, has also been linked to the dystrophin gene. Myotonic dystrophy is an autosomal dominant disease that commonly involves the myocardium and the conduction tissue, resulting in conduction defects and heart failure. Sudden cardiac death is the most common cause of mortality in patients with myotonic dystrophy. Recently, the myotonin protein kinase gene located on chromosome 19 was identified as the gene responsible for this disease. Expansion of the number of trinucleotide repeats in the myotonin protein kinase gene results in myotonic dystrophy. Mutations in mitochondrial DNA have been associated with hypertrophic and dilated cardiomyopathy. The inheritance of mitochondrial cardiomyopathy is maternal and the disease is associated with certain systemic disorders.

Publication types

  • Review

MeSH terms

  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Hypertrophic / genetics*
  • Dystrophin / genetics
  • Humans
  • Muscular Dystrophies / genetics
  • Mutation
  • Myosins / genetics
  • X Chromosome

Substances

  • Dystrophin
  • Myosins