Genetic Testing

Genetic testing (also known as DNA testing) is the process of examining a person’s DNA. For Duchenne, the dystrophin gene is checked to see if any changes or mutations are present that would prevent the gene from working properly. Genetic testing is usually performed on a blood or saliva sample.

PPMD’s Free Genetic Testing Program

PPMD has a genetic testing program called Decode Duchenne that provides FREE genetic testing to eligible individuals. The application and testing process is fast and easy, and includes interpretation of results and counseling. Learn more about PPMD’s Decode Duchenne program.

Why is genetic testing so important?

In today’s world where diagnoses are made earlier, care and management is better, and new therapies are on the horizon, genetic testing is more important than ever before. In the past, testing for Duchenne was performed using a CK blood test in combination with a muscle biopsy, but today genetic testing is the gold standard for diagnosing Duchenne.

Here are three reasons why it is important to have genetic testing:

1. To confirm your diagnosis: Genetic testing will confirm if you have Duchenne, or if you may have another type of muscular dystrophy that shares some of the same features as Duchenne, such as Becker and others.
2. To enable testing of family members: Once the mutation in a family is known, then other family members can be tested to determine if they are carriers of the gene mutation. Genetic testing is the best method for performing accurate carrier testing.
3. To determine what mutation-specific therapies may benefit you: Many therapies in development and/or approved for Duchenne are “mutation-specific”, meaning they will only benefit individuals with certain mutations. You must know your mutation in order to participate in a clinical trial and to access any current or future mutation-specific therapies. If you’ve never had genetic testing or if you need repeat genetic testing, remember that our Decode Duchenne program provides FREE genetic testing to eligible individuals.

How do I start the genetic testing process?

• If you have a child with a known or suspected diagnosis of Duchenne, your child’s neurologist will most likely order genetic testing or he/she will refer you to a geneticist and/or genetic counselor. If genetic testing has not been mentioned, you should have a conversation with your child’s doctor and request the testing.
• If you are female with a family history of Duchenne and you would like carrier testing, your healthcare provider or OB/GYN can order carrier testing or they can refer you to a genetic counselor in your area.

What if my family cannot afford genetic testing?

PPMD has a genetic testing program called Decode Duchenne that provides FREE genetic testing to eligible individuals. The application and testing process is fast and easy, and includes interpretation of results and counseling. Learn more about PPMD’s Decode Duchenne program.

What is the best laboratory method for genetic testing?

There are many different laboratory methods for genetic testing, and the methods are constantly evolving and improving over time. Often the best method to use depends on your family history and whether the mutation in the family is known.

If the mutation in your family is known

Your doctor or genetic counselor should order known familial mutation testing. This testing only looks for the specific mutation that has already been identified in your family. This is faster and less expensive than examining the entire gene. The method used for the known familial mutation testing will depend on the mutation in your family.

If the mutation in your family is not known

Your doctor or genetic counselor should order these tests:

• First, a test to look for large deletions and duplications in the dystrophin gene should be ordered because these are the most common types of mutations. The most common methods for finding deletions and duplications are called CGH array testing and MLPA testing. Older methods that are no longer widely used include PCR and Southern blot testing.
• Second, if no deletion or duplication is found, another test must be ordered to look for smaller changes and point mutations in the gene. The method for finding these smaller mutations is called Sanger gene sequencing.

A newer technology is emerging that combines the ability to detect deletions, duplications, and smaller point mutations in one test. This method is called next generation sequencing (NGS) and it is available in some laboratories.

What do my genetic test results mean?

If a mutation in the dystrophin gene was found

This means that the person who was tested has Duchenne. Usually the lab can predict based on the type of mutation whether a person will have symptoms of Duchenne. If the lab cannot make a prediction based on the mutation, and the doctor cannot determine if it is Duchenne based on the symptoms, a muscle biopsy can usually provide that information.

• Finding a mutation may also mean that the person qualifies for certain clinical trials or new treatments. If you or your child have a known mutation, we encourage you to create an account on The Duchenne Registry. Registering will provide you access to our most current information on research studies and will provide researchers with valuable data that will help in our fight to end Duchenne.

If a mutation in the dystrophin gene was not found

This does not necessarily mean that a person does not have Duchenne. If you have had comprehensive genetic testing, including testing for deletions, duplications, and small mutations (estimated to detect 95-99% of cases of Duchenne muscular dystrophy) and no mutation is found, there is additional testing that can be done:

• Your doctor may decide to order a muscle biopsy as the next step. The biopsy should be ordered with immunoblot and immunostaining for dystrophin, to confirm the diagnosis of Duchenne. These techniques allow doctors to see exactly how much dystrophin protein is present in the muscle tissue. No dystrophin protein usually means Duchenne, whereas some dystrophin protein (but not the normal amount) usually means Becker.
• Your doctor may also consider additional testing on the muscle tissue, such as cDNA or mRNA testing. These techniques allow doctors to see if the dystrophin gene is being transcribed properly into mRNA in the muscle tissue. Rather than looking at the dystrophin gene (which has already been analyzed), they are looking at the next step in the pathway for producing dystrophin protein.

If your diagnosis is confirmed and you have had comprehensive genetic testing and all of the tests have been negative, you are very likely one of the 1-5% of people for whom lab methods cannot yet find the mutation. Keep in touch with your neuromuscular center or genetic counselor because genetic testing is continually improving and your mutation could be identified using newer methods in the future.

Who else in my family needs to have genetic testing?

Identifying a mutation allows other people in the family to find out if they have the same mutation. Female relatives may be interested in genetic testing to find out if they are carriers. Carriers have a chance of having children with Duchenne and they themselves can have signs of Duchenne such as cardiomyopathy. Read more about carriers.

Usually the mother of a child with Duchenne will be tested first to determine if she is a carrier:

If the mother tests negative for being a carrier

It is likely that the gene mutation started new in her child. However, due to the small chance of germline mosaicism (when a mother carries the gene mutation in some of her egg cells but not her blood cells), her other children should be tested. If she has other sons and they are older and not showing any signs of Duchenne, they will likely not need to be tested, but all daughters should be offered carrier testing.

If the mother tests positive for being a carrier

Her other children should be offered testing (except sons who are older and not showing any signs of Duchenne). In addition, the mother’s sisters, her mother, and her maternal aunts should be offered testing.

A genetic counselor can review your family history in detail and determine exactly who needs testing. A genetic counselor can also help coordinate this testing and explain the results to you. Learn more about genetic counseling.