Functional consequences of mutations in the myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy.

The primary cause of familial hypertrophic cardiomyopathy (FHC) has been attributed to mutations in the genes that encode the contractile proteins of the muscle cell. A majority of these mutations have been found in myosin, the principal component of the thick filament. Most in vitro studies have concluded that FHC mutations cause a loss of function in the biochemical and mechanical properties of myosin. Hypertrophy would then follow as a compensatory mechanism to raise the work and power output of the failing heart. Several recent studies, however, have thrown this mechanism into doubt by providing evidence that FHC mutations in the myosin heavy chain (MHC) can enhance the functional properties of myosin. This review discusses the problems encountered in reaching a definitive answer on the effect of MHC mutations.