Variability in the ratio of mutant to wildtype myosin heavy chain present in the soleus muscle of patients with familial hypertrophic cardiomyopathy. A new approach for the quantification of mutant to wildtype protein.

The ratio of mutant to wildtype myosin heavy chain (beta-isoform, beta-MHC) in the soleus muscle of patients with familial hypertrophic cardiomyopathy was determined by a combination of HPLC, mass spectrometry and capillary zone electrophoresis. In two patients, one with a Val 606 Met mutation and another with a Gly 584 Arg mutation, the fraction of mutant beta-MHC was only 12+/-6% and 23+/-0.7% of total beta-MHC, respectively. These results demonstrate the necessity to determine the ratio of mutant to wildtype protein for the interpretation of functional studies on biopsy material from heterozygous patients with an inherited disease.