Carrier Testing
Why is genetic carrier testing important?
Genetic testing is the best method for accurately confirming if a woman is a carrier or if she is unlikely to be a carrier.
We know that females with a DMD variant are at risk to develop symptoms related to dystrophinopathy, including cardiac changes and skeletal muscle weakness. Carriers should be evaluated regularly by a doctor who is familiar with dystrophinopathy. Regular cardiology appointments are necessary and referrals to other specialists may be needed. Learn more about Carrier Symptoms and Care.
If someone is confirmed to be a carrier, they may want to use that information to explore options for growing their family. Learn more about reproductive options for carriers.
Finally, genetic testing is important because it may help to identify others in the family who would need testing.. It is important to share information about the specific genetic variant found in your family with your relatives so they can pursue testing if desired.
PPMD’s Decode Duchenne genetic testing program provides free genetic testing to people in the dystrophinopathy community. For more information regarding our free genetic testing program, click here.
Who should consider carrier testing?
Once dystrophinopathy has been diagnosed in a family, it is important for family members to talk with a genetic counselor. A genetic counselor will take a detailed family history and will determine who in the family may need genetic testing.
All women who could be carriers based on their family history should be offered carrier testing. This includes women with:
- sons or brothers with dystrophinopathy
- uncles or cousins on their mother’s side of the family who have dystrophinopathy
- mothers or sisters who are carriers
- aunts or cousins in their mother’s side of the family who are carriers
Additionally, girls or women with unexplained high CK (creatine kinase), muscle symptoms, or heart symptoms might also be candidates for DMD gene testing. When someone is tested based on their symptoms or CK levels, the genetic testing often includes more genes than just DMD.
What are the types of tests used to identify carriers?
Genetic testing is the best method for performing accurate carrier testing. Genetic testing is quicker and more accurate when the genetic variant in the family has been confirmed first in an affected relative. If the variant in the family is not known and/or there are no living affected relatives, carrier testing can still be done, but it will require analyzing the entire gene rather than looking for a specific variant. It is important to note that some complex genetic variants may not be picked up by standard genetic testing methods.
In the past, CK testing and/or muscle biopsy were used for carrier testing, but these are no longer the preferred methods. CK levels do not accurately predict someone’s chance of having a genetic variant or developing symptoms and are often higher in child and adolescent carriers than in adult female carriers. CK levels also may be increased for reasons other than muscular dystrophy, such as strenuous activity or sickness. Many carriers have normal CK levels. Muscle biopsies on carriers are generally avoided because they are invasive (a biopsy requires removing a piece of muscle tissue so it can be studied under a microscope) and less accurate than genetic testing.
How is carrier genetic testing done?
Carrier testing is done on a blood or saliva sample. There are different lab methods that can be used for carrier testing. The method for carrier testing should be determined by the family situation, including whether the variant in the family is known and the individual’s family history.
- If the variant in the family is known, targeted testing should be completed to look for that specific variant.
- If the variant in the family is not known because the person with dystrophinopathy has not had testing, it is best to test the affected person first using a blood or saliva sample.
- If the variant in the family is not known and there are no living affected relatives to test, a comprehensive testing plan can still identify most (but not all) carriers.
If an affected individual completed genetic testing in the past and no variant was found, it might be appropriate for them to test again using new and improved tests, which can identify more genetic variants. PPMD’s Decode Duchenne program provides free repeat genetic testing to individuals with Duchenne and Becker, regardless of their age.
Can carrier testing identify germline mosaic carriers?
Women with germline mosaicism will not be found to be carriers via genetic carrier testing, because carrier testing is done on blood or saliva cells. Women with germline mosaicism only have variants in some of their egg cells, which will not show up on a blood or saliva test.
Because lab testing cannot identify germline mosaicism, healthcare providers are left to assume that germline mosaicism explains most cases where a woman has negative genetic testing but has more than one affected child.
All women who have a child with dystrophinopathy and negative carrier testing have a chance to have germline mosaicism.
When should carrier testing be done?
Carrier testing should be offered to all at-risk adult women with a family history of dystrophinopathy. In the past, carrier testing was generally not performed on minors. However, with increasing knowledge of the potential for symptoms in carriers, and with genetic testing in general becoming more prevalent, carrier testing on minors is now more common.
For adolescents, it is important to consider their maturity and to make sure they get the right support and information before and after testing. If you are interested in carrier testing for a minor in your family, please speak with their doctor or a genetic counselor to review the pros and cons of testing.
When discussing testing for currently asymptomatic minors, one consideration should be the potential impact on specific types of insurance. The Genetic Information Nondiscrimination Act (GINA) provides protection in regard to health insurance and employment. However, this does not provide protection for life insurance, long term care, or disability insurance. You may find more information on GINA here.
For more information regarding PPMD’s free genetic testing program, Decode Duchenne, click here.
What do results from carrier testing mean?
- Positive genetic testing confirms the presence of a DMD variant, and the impact of that variant may vary from person to person.
- If the familial variant is known and carrier testing does not find the familial variant, that means that the woman is very unlikely to be a carrier. Learn more about germline mosaicism, which can increase the risk for having a child with dystrophinopathy even if a mother is not a carrier.
- If the familial variant is not known and appropriate carrier testing does not identify the variant, it reduces the chance that the woman is a carrier, but does not make the chance zero. This is the most difficult type of result for healthcare providers and families to interpret. A genetic counselor can help you understand this result and what additional testing might be useful.
If you are found to be a carrier, please consider joining The Duchenne Registry. Started by PPMD in 2007, The Duchenne Registry has always collected data on female carriers. The data you share helps advance research by providing a better understanding of the impact of being a carrier and the significance of different types of genetic changes.
