Mutations in HCM genes cause a heart disease called hypertrophic cardiomyopathy, which can lead to sudden cardiac death. Early genetic testing of people who might be at risk is important to ensure treatment and monitoring can help prevent heart attack or death.
What is the HCM Gene?
The HCM gene is not one single gene, but rather a collection of genes which are known to be involved in the development of a heart condition called hypertrophic cardiomyopathy.
More than a dozen different genes have been identified and added to the list of those which can cause the disease when mutations arise. Collectively these genes code for proteins involved in what is called the cardiac sarcomere. The cardiac sarcomere is a network of proteins which extend throughout the heart muscle and coordinate its rhythm. Mutation in any of the cardiac sarcomere proteins can lead to hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy is an abnormal thickening of the heart muscle which causes valves to work incorrectly, or causes the obstruction of blood flow. Symptoms of this disease include chest pain, shortness of breath, heart palpitations, dizziness, and fainting. Hypertrophic cardiomyopathy is a common cause of sudden cardiac death in young people, especially young athletes.
HCM Gene Mutations
In the known genes which contribute to hypertrophic cardiomyopathy, several hundred different mutations have been identified. Around two-thirds of all cases of hypertrophic cardiomyopathy are due to mutations in one of three genes, which code for proteins called the beta -myosin heavy chain, the cardiac troponin T, and myosin binding protein-C.
Transmission of HCM Gene Mutations
Hypertrophic cardiomyopathy is an autosomal dominant condition. The term autosomal means that the genes which can cause the disease are located on autosomes, and not on sex chromosomes. As a result, this condition can affect females and males in equal numbers. The term dominant means that only one copy of the mutated gene needs to be inherited for the disease to develop.
HCM gene mutation carriers have a 50% chance of passing the gene on to a child, and statistically, half the children of a carrier will inherit the mutation. This is true whether or not the parent has disease symptoms or has been diagnosed.
Some people can develop hypertrophic cardiomyopathy even if there is no family history of the disease. In these cases the genetic mutation is generally a spontaneous occurrence, rather than an inherited mutation. When this happens the affected individual has a 50% chance of passing the mutated gene on to each of his or her children.
Genetic Testing for HCM Gene Mutation Carriers
When someone is diagnosed with hypertrophic cardiomyopathy that is not known to run in the family, it is important for immediate family members to have genetic testing to determine whether any other family members have the mutated gene.
For any given individual, any of his or her first degree relatives might be affected. This includes the individual’s parents, siblings, and children. If the individual’s siblings are affected, the children of those siblings might also have inherited the mutated HCM gene. This testing is important for all family members who might be affected, even if they have no symptoms, to identify people who are at risk of heart problems.
Genetic testing of potential HCM gene mutation carriers involves testing an individual’s blood to determine whether any specific mutations are present. Tests are done in one or two separate panels. The first tests for the most common HCM mutations, while any subsequent panels test for mutations which are uncommon.
Someone who is confirmed to have a mutated HCM gene might undergo cardiac evaluation that includes a physical exam and cardiac work-up to determine the extent of the disease.
References
Brigham and Women’s Hospital Cardiovascular Genetics Center: Understanding the Basic Genetics of HCM (PDF)
Harvard Medical School Center for Genetics and Genomics: Hypertrophic Cardiomyopathy Genetic Test
PGx Health Familion Genetic Testing: Cardiomyopathy Patient Information
University of Medicine & Dentistry of New Jersey: Hypertrophic Cardiomyopathy
