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BookmarkScienceDaily (Nov. 12, 2007) — Familial Hypertrophic Cardiomyopathy (FHC), the leading cause of sudden death in athletes and young people, is a genetic disorder of the heart that is characterized by an increased thickness in tissue of the left ventricle.
FHC is thought to be caused by a mutation in the myosin heavy chain, one of the components of muscle cells in the heart, which causes a disruption in the normal alignment of muscle cells otherwise known as myocardial disarray.
One of the deadliest forms of FHC is caused by the R403Q mutation, which kills 50% of those affected individuals by 40 years of age. A study conducted by scientists at the Burnham Institute for Medical Research (Burnham Institute) in La Jolla, CA provides new structural evidence that the disarray at the molecular level caused by the R403Q point mutation in myosin is linked to the characteristic misalignment of muscle cells in FHC.
The scientific group, led by Dr. Dorit Hanein (Burnham Institute), used smooth muscle myosin to investigate the structural effects of the R403Q mutation.
The group concluded that this point mutation severely disrupts actin-myosin interactions as compared to those in wildtype myosin. While myosin normally attaches to the actin filament at a fixed angle, the mutated myosin displayed a wide variety of angles at the attachment sites, thus demonstrating a structural basis for the change in function of the mutant myosin.
Dr. Hanein illustrates how the conformational instability within the sarcomere affects ability of the heart to function properly and may lead to compensatory hypertrophy in cardiac muscle tissue, which is a trademark phenotype of FHC.
This study allows for a better understanding of the origination of FHC at the molecular level, which may open doors for the development of drugs to treat this disorder in the future.
Dr. Dorit Hanein is an Associate Professor within the Infectious Diseases Program at the Burnham Institute for Medical Research. The study was conducted in collaboration with the University of Vermont Department of Molecular Physiology and Biophysics. It was recently published in PloS One.
Story Source:
Adapted from materials provided by Burnham Institute.
Note: If no author is given, the source is cited instead.
