Overview of Project 3:
Familial hypertrophic cardiomyopathy (HCM) is inherited as an autosomal dominant disease that is caused by dominant-negative-acting sarcomere protein gene mutations. Mutations in beta-cardiac myosin heavy chain, cardiac actin, cardiac troponin T, alpha-tropomyosin, cardiac troponin I, cardiac myosin-binding protein C, and the myosin light chains have all been shown to cause HCM. We hypothesize that the number of sarcomere protein gene mutations that can cause HCM is finite, and we propose to identify the complete complement of such mutations. Knowledge of this complete set of mutations will provide insights into the mechanisms by which these mutations cause cardiac disease as well as provide useful tools for the genetic diagnoses of these conditions. In order to define the complete set of disease-causing sarcomere protein gene mutations, we are screening the eight genes encoding sarcomere protein genes in HCM patients. This complete set of HCM-causing mutations will also allow more rapid and less expensive diagnostic tests for HCM.
A second goal of these studies is to provide a database that allows correlation of HCM severity and mutation. Many HCM-causing mutations are found in patients with several affected family members. These affected family members can provide useful clinical information regarding the severity of a particular mutation. During the first three years of this study limited family information has been provided. However, we have developed procedures which should allow the more rapid collection of additional family information over the next several years.
Methodology
View our methods and protocols
for clinical evaluations, PCR and sequencing reactions, data analysis, and mutation confirmation.
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Mutation Database
In keeping with our policy of making our research tools available to the community at large, we have compiled a
database
of published information about known sarcomere mutations, as well as exon, PCR primer, and amplimer data for each
of the genes we are examining.
Individuals interested in participating in a research study may contact
Barbara McDonough, R.N.,
for more information.
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