The Mechanism Of Mutations In The Cardiac Myosin-binding Protein C Gene Causing Hypertrophic Cardiomyopathy

Genetic studies have shown that familial hypertrophic cardiomy-opathy (FHCM) is an autosomal dominant disorder of heart muscle. One of the mutations in genes encoding sarcomeric, proteins can result in this disease. Seven different disease genes have been identified by means of linkage mapping or candidate gene analysis from the FHCM pedigrees, the process to cause FHCM is not entirely clear, but there are two hypothesises : (1)The mutations act as poison polypeptides that interfere with the function of wild-type peptides, thereby resulting in a "dominant negative" effect; (2)The mutations function as null alleles Leading to an imbalance in stoichiometry because null alleles could not express or produce unstable polypeptides that are not incorporated into myofibrils.It is reported that myosin could bind to the C10 IgI domain of MyBPC in C-terminal. This paper was aimed at monocloning the human cardiac wide-type complementary DNA (cDNA),preparing and expressing five different mutant MyBPC genes (such as inserting or shipping or repeating ones),comparing the myosin-binding abilities...