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.
Nier
V
V
Molekular- und Zellphysiologie, Medizinische Hochschule Hannover, D-30625, Hannover, Germany.
Schultz
I
I
Brenner
B
B
Forssmann
W
W
Raida
M
M
D019943:Amino Acid Substitution; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019075:Electrophoresis, Capillary; D006579:Heterozygote; D006801:Humans; D013058:Mass Spectrometry; D018482:Muscle, Skeletal / Q000737:chemistry*; D018995:Myosin Heavy Chains / Q000032:analysis* / Q000235:genetics; D010446:Peptide Fragments / Q000032:analysis; D017354:Point Mutation; D020033:Protein Isoforms / Q000032:analysis* / Q000235:genetics
D010446:Peptide Fragments; D020033:Protein Isoforms; D018995:Myosin Heavy Chains