Home > Advanced Duchenne/Becker Muscular Dystrophy Genetic Testing

Advanced Duchenne/Becker Muscular Dystrophy Genetic Testing

Genetic Testing for Duchenne and Becker Muscular Dystrophy

Genetic tests find changes, called mutations, in genes that cause disease. These tests can be a helpful tool in confirming a disease diagnosis. Different types of mutations may cause a single disease. Some drugs are more effective for certain types of mutations and some drugs only work on certain mutation types. Knowing what type of mutation is present may predict how a person will respond to certain drugs. In deciding to have or not have a genetic test, it is helpful to understand a little about how genes work, what types of mutations genes may carry, and how genetic testing is performed.

Background
Cells are specialized small units that make up all living things, and the human body contains trillions of cells. There are many different types of human cells, including brain cells, liver cells, and muscle cells. Every cell contains 20,000 to 25,000 genes. Genes, made up of DNA, are the “blueprints” of the cell and tell our body how to make proteins. Proteins form the structure of the cells and perform most important functions in the human body. Proteins produce traits – such as eye color, foot size, and height –and can be passed from parent to child.

An important protein made in muscle cells is dystrophin. This protein allows muscle cells to hold their shape and structure. Without normal dystrophin, muscle cells become fragile and break down, and this leads to muscle weakness. This lack of normal dystrophin is the cause of Duchenne muscular dystrophy (DMD), and is also the cause of a milder form of the disease, Becker muscular dystrophy (BMD).

A change or mutation in the genetic blueprint can lead to a loss of dystrophin. A mutation may also result in production of a dystrophin protein that is short and/or does not work properly so that it does not serve its purpose as a building block for muscle cells. Several types of mutations within the DNA of the dystrophin gene can lead to DBMD. They include:

  • Deletion – a large section of the DNA blueprint for dystrophin is missing.
  • Duplication – a large piece of dystrophin DNA is repeated.
  • Insertion – a small extra piece of DNA is added to the dystrophin gene.
  • Missense – a segment of the genetic code is changed, which leads to an error in the dystrophin protein.
  • Nonsense – a segment of the genetic code is changed and is read as a premature "stop signal" in the gene, so that cells stop making the dystrophin protein or make an incomplete protein.

Potential Uses of Dystrophin Genetic Testing
Genetic testing can confirm whether or not someone has DBMD and can indicate the specific type of genetic mutation (deletion, duplication, insertion, missense, or nonsense) that is causing DBMD. This knowledge may make a person eligible to participate in a clinical trial of a drug designed to overcome their specific type of mutation.

Other companies are testing drugs that may be useful in treating other types of mutations, such as deletions. Researchers are also working to develop drugs that may be able to overcome the lack of dystrophin by increasing production of other types of proteins that can make muscle cells less fragile.

Knowing the type of dystrophin mutation may help patients and families choose between clinical trials or treatment options. Carefully choosing a treatment plan not only increases the chance of success, but also avoids exposure to a drug that may have little or no chance for benefit and may unnecessarily expose patients to harmful side effects.

CFTR gene testing can be performed on individuals who are suspected of having cystic fibrosis, on siblings of those with cystic fibrosis and on mothers and fathers who believe they may be carriers of the disease and are concerned they might pass it on to their children. Carrier testing is especially important for couples of northern European and Ashkenazi Jewish descent, as the frequency of the CFTR mutation is higher in these populations. It is also important to note that in individuals with other ancestry, the mutations are often different and routine testing may not be as reliable as in the Caucasian population.

Performing Dystrophin Genetic Testing
To perform the gene test for DBMD, a single routine blood sample is collected. In most cases, a primary doctor can order the test. To arrange for testing, the doctor can contact a gene-testing laboratory (see below) to get instructions on the type of blood collection tube to use and the details of where to send the blood sample. Often the doctor's office can also provide information on the cost of the test and whether health insurance will provide full or partial coverage.

Once the sample is sent to the gene-testing laboratory, the laboratory will check to see if a mutation is present in the dystrophin DNA. The laboratory will also test for the type of mutation and its location within the dystrophin gene.

Different technologies are necessary to detect the various mutation types and may require a two-step process. The laboratory will first test for deletions and duplications because these are the most common mutations. Deletions and duplications account for over half of the mutations in the dystrophin gene in DBMD. If no deletions or duplications are found in the first test, the healthcare provider will then consider a second test, called gene sequencing or sequence analysis. The second test looks for other types of gene changes, including insertions, missense, and nonsense mutations. Usually laboratories charge separately for each test.

Genetic test results are sent to the doctor who ordered the test. Depending upon whether one test or both tests are required, the results are normally available in 3 to 8 weeks.

Deciding Whether to Have Dystrophin Genetic Testing
As noted above, genetic testing can have advantages. However, in some situations, the knowledge that comes with testing may bring concerns. Family members may differ in their responses to genetic test results. These differing responses may result in changes in relationships among family members. Choices regarding reproductive decision-making and options for prenatal testing are things that every family should consider before having testing. Insurance companies vary on coverage for genetic testing, and families should consider the cost of testing. It is important to for each family to consider the advantages and disadvantages of the test before it is performed.

Genetic Testing Resources
Physicians who treat cystic fibrosis will generally be aware of laboratories that perform genetic testing. Laboratories that perform testing may also be located through GeneTests (www.genetests.org), a web site sponsored by the United States National Institutes of Health. Once on this site, click on the Laboratory Directory link at the top of the page to find a list of genetic testing laboratories. Note that since listing on the GeneTests website is voluntary, not all laboratories may be listed. To find a specific laboratory doing genetic testing for DBMD, search for the disease name (Duchenne or Becker) or for dystrophin.

GeneTests can be searched for the location of a laboratory in the country or region of the person to be tested. Not all countries have genetic testing laboratories. (http://www.orpha.net/consor/cgi-bin/index.php) is a similar resource for European laboratories. If the patient's physician or genetic counselor cannot recommend a nearby laboratory, it may be possible to have blood drawn near the patient's home and shipped to a laboratory for testing. It is important to contact the laboratory before collecting the blood sample to find out the procedure.

Additional Genetics Resources
In addition to the doctor, speaking with a genetic counselor may benefit the patient and his or her family. Genetic Counselors can help with the decision-making process and explain or coordinate testing. Genetic counselors can help interpret the results of the gene sequence test; provide guidance on the best use of the information gained from the test; and answer questions about genetics in general and the types of tests that are available.

Many online resources offer information on genetics and genetic testing: