Genetic counselors, whether they are part of PPMD's DuchenneConnect team or part of your local care team, are an excellent resource to consider when you have questions about genetic test results for Duchenne and Becker muscular dystrophy.
Today, I’d like to tackle the topic of re-testing:
Some quick highlights:
An in-depth look:
Accurate genetic test results for Duchenne and Becker are important for many reasons:
Since the late 1980s, when the Duchenne gene (dystrophin, DMD) was first discovered, genetic testing for Duchenne and Becker muscular dystrophy has come a long way.
The first genetic tests for Duchenne could only identify certain deletions. Today, testing can identify deletions and duplications throughout the entire gene as well as find small “point” mutations. DuchenneConnect co-director Ann Martin notes, “these advances mean that a genetic diagnosis is available to many more families today than in decades past. Because genetic testing technology has changed so much, some people may benefit from repeating their testing to confirm their exact genetic change.”
Determining who needs re-testing, however, is a more complicated question.
First, its important to know that a person’s mutation can’t change over time. Lauren Morgenroth, Genetic Counselor for the Cooperative International Neuromuscular Research Group (CINRG), explains: “Unlike your blood sugar or cholesterol levels, your genes and DNA are not something that can fluctuate day to day. The genetic changes that cause Duchenne and Becker are present in your DNA from birth.” For this reason, re-testing isn’t intended to find different results when a mutation is already known. Instead, the goal is to better define a result or locate a mutation that couldn’t be found with older technologies. Many people wonder what “older” means and ask: is there a test date that is automatically too old? Lauren advises that “although individuals with older reports that use outdated technologies may need to undergo re-testing, there is no exact date cut-off for this, and not all individuals with “old” tests will need re-testing.”
It’s true: because new testing methods aren’t started by all labs at the same time, we can’t rely on just a test date to decide who needs to be re-tested. Instead, the need for re-testing is based on a person’s current results and the type of technology used for their test.
Re-testing can be considered for several groups of people, including those who:
Importantly, all cases should be reviewed on a case-by-case basis to make a re-testing decision.
Why might these situations warrant re-testing?
These are situations where re-testing could help someone find their mutation or help someone confirm the size of their mutation more accurately. Scenario 1 is an example when more testing could find a mutation that previous technologies couldn’t. If a person has a small “point” mutation, where just one or a few letters in the DNA are changed, then deletion/duplication tests won’t be able to find it. Only sequencing can locate this change.
Scenario 3 is an example where re-testing can confirm a mutation’s exact size. For example, if a test finds a deletion of exons 50-53, but didn’t check exons 49 and 54, we don’t know whether or not exons 49 and 54 are also deleted. Re-testing with newer technologies would confirm the size of the mutation by telling us exactly how many exons are deleted. It is important to know the exact location of where the mutation starts and stops, since this is a requirement for certain research studies that focus on specific exon mutations.
Even deletion/duplication tests that do check all 79 exons are not always created equal. Some of these testing technologies, including Southern Blot, multiplex PCR and MLPA, have limitations in their ability to confirm either duplications or single exon changes. For that reason, groups 4 and 5 above can consider re-testing with a newer technology called array CGH to confirm that their mutation is correct. More information about the different types of tests used for Duchenne can be found in the “Understanding Genetic Testing” section of DuchenneConnect.
How do I find out if I need re-testing?
If you’re wondering whether you or your child might need re-testing, you can first look back at the original test result for clues. You can look for key words like “MLPA,” “Southern Blot,” or “multiplex PCR”, which is sometimes listed as just “PCR amplification.” You can also see if the report only lists some exons as being tested, or if it provides a list of “probes” that were tested. If you’ve had negative deletion/duplication testing, check to see if you can find a report that mentions gene sequencing.
Genetic test reports can be difficult to read, so don’t worry if you aren’t sure about what you see. If you think you might need re-testing or aren’t sure, contact your doctor or genetic counselor. They can review the result with you, explain what they see, and confirm if more testing is needed.
Will technology keep changing?
Over time, genetic testing capabilities continue to improve. These ongoing improvements might especially help those who have had negative sequencing and still don’t know their mutation. Some labs are now offering enhanced sequencing tests that look for mutations deep within the introns, which are sections of DNA between the exons. In these situations, Dr. Madhuri Hegde, executive director of the Emory Genetics Laboratory, suggests considering repeating sequencing by ordering a muscular dystrophy panel that includes all 79 exons of the DMD gene, flanking intron/exon boundaries of at least 20 base pairs, and contacting the testing laboratory to ask if their single gene DMD test or neuromuscular panel with the DMD gene includes deep intronic mutations shown to be disease causing in the literature.” More information about Emory’s panel testing is available at geneticslab.emory.edu.
How DuchenneConnect can help:
DuchenneConnect has three certified genetic counselors, myself included, who can help with many different test questions. We can help you obtain a copy of your genetic test report if you don’t have your own copy, review the results with you, and help decide if re-testing is needed. If re-testing is needed, or if you still need genetic testing for the first time, our Decode Duchenne testing program can provide free testing for eligible individuals. Decode Duchenne provides free testing to those who have symptoms of Duchenne or Becker, cannot currently afford testing, and are legal residents of the United States or Canada. Although free carrier testing is not available through the program at this time, Decode Duchenne does provide access to reduced testing rates and genetic counseling to those with carrier testing questions.
Don’t forget, you can also upload your genetic test report to your DuchenneConnect profile. This not only helps connect you to mutation-specific research and provides valuable information to researchers, but also ensures you always have a saved copy of your report that is easy to access.
Today, check to make sure that you have a copy of your genetic test result, upload it in DuchenneConnect, and contact us at firstname.lastname@example.org or 888.520.8675 option 1 if you have any questions. We are here to help!
Thank you to Dr. Madhuri Hegde, Lauren Morgenroth, and Ann Martin for lending their expertise to this blog, with a special thank you to Dr. Hegde for validating the list of situations that warrant re-testing.