Hypertrophic cardiomyopathy (HCM) is a genetically inherited heart disease. It causes
thickening of heart muscle, especially the chamber responsible for pumping blood out of the
heart, the left ventricle. Hypertrophic cardiomyopathy (HCM) is the most important cause of
sudden death in apparently healthy young people.
A genetic test called linkage analysis is used to locate genes causing inherited diseases
like HCM. Linkage analysis requires large families to be evaluated clinically in order to
identify the members with and without the disease.
In this study researchers will collect samples of DNA from family members of patients with
HCM. The diagnosis of the disease will be made by history and physical examination,
electrocardiogram (12 lead ECG), and ultrasound of the heart (2-D echocardiogram). The
ability of the researchers to locate the gene responsible for the disease improves with
increases in the size of the family and members evaluated.
In order to continue research on the genetic causes of heart disease, researchers intend on
studying families with specific genetic mutations (beta-MHC) causing HCM. Researcher plan
to also study families with HCM not linked to specific gene mutations (beta-MHC).
Hypertrophic cardiomyopathy (HCM) is the most important cause of sudden death in apparently
healthy young individuals but its clinical manifestations are highly variable. Linkage
analysis is used to localize a gene causing an inherited autosomal dominant disease, such as
HCM. Linkage analysis requires that large families be evaluated clinically to determine the
members with and without the disease. For this study, DNA needs to be extracted from blood
samples of family members. The presence of the disease is determined by history and
physical exam, 12 lead ECG and 2-D echocardiogram. The likelihood of localizing the gene
increases with the size of the family and the number of members evaluated. The beta myosin
heavy chain (beta-MHC) gene has been shown to be responsible for HCM in 10%-30% of affected
kindreds. Other linage studies have shown that there are at least 3 other genes which cause
HCM in other kindreds, but these genes are presently unknown. We have identified 13 unique
mutations in the beta-MHC gene which cause the disease in 17 kindreds. This has allowed us
to demonstrate skeletal muscle involvement, study the abnormal physiology which is a
consequence of the mutations, make pre-symptomatic diagnosis, and redefine the natural
history of the disease. In order to continue our clinical and laboratory studies of this
disease over the next 3 years, it is our intention to identify 50 additional HCM kindreds,
with approximately 50 members each, that have beta-MHC gene mutations. During this time, in
order to map other HCM genes, we will also evaluate at least 6 families, of approximately
300 members each, in which the disease is not linked to the beta-MHC gene.
Patients with a family history of hypertrophic cardiomyopathy are eligible.