Why mutations matter Scientists have recorded more than 1, mutations in the DMD gene in people with the Duchenne and Becker forms of muscular dystrophy. Learn more about genetic testing. Learn More. Not sure what a Duchenne diagnosis means for your family? Find out how genetic counseling can help. Need help understanding your deletion? Use our exon deletion tool. We need your input! Thank you in advance!
If you or your child have a deletion mutation, you have probably heard the terms in-frame and out-of-frame. Sometimes this is referred to as the reading frame rule. A deletion is in-frame if the reading frame of the gene is preserved and not disrupted, so some dystrophin protein can be made. The protein may be shorter than normal, but it is still functional. In-frame deletions typically result in Becker muscular dystrophy, which usually has a more mild presentation compared to Duchenne because there is some dystrophin protein present in the cells.
A deletion is out-of-frame if the reading frame is completely disrupted, so that no dystrophin protein can be made. Out-of-frame deletions typically result in Duchenne muscular dystrophy, which usually has a more severe presentation compared to Becker because there is no dystrophin protein present in the cells.
It is important to remember that this reading frame rule is not always perfect. There are some out-of-frame deletions that cause Becker, and some in-frame deletions that cause Duchenne. Please speak with your doctor or genetic counselor if you have questions. Males have only one copy of the X chromosome from their mother and one copy of the Y chromosome from their father. Females, on the other hand, have two copies of the X chromosomes..
Since females have two copies of this gene, if one copy does not work, they have a second back up copy to produce the dystrophin protein.
A woman who has a genetic change in one of her two copies is said to be "a carrier" of Duchenne muscular dystrophy. Carriers do not have Duchenne muscular dystrophy and most are unaware that they even carry this change in their genetic material unless they have a family history. However, recent studies have shown that some carrier females approximately 20 percent will show symptoms of DMD, including muscle weakness and cardiac abnormalities.
With an X-linked recessive condition, the chance of passing on the changed non-working copy of the gene to a child is different for males and females. Females who carry the changed copy of the gene have a 50 percent chance of passing it on with each pregnancy. Thus, there is a 25 percent chance of having a affected child with DMD eg. However, in the remaining third of individuals with DMD, the change in the dystrophin gene is a new genetic change, or de novo change and about 10 percent of new mutations are due to gonadal mosaicism.
Gonadal mosaicism refers to a condition where an individual has two or more cell populations that differ in genetic makeup in their eggs or sperm. If a male with DMD were to have children, all of his daughters would be carriers and none of his sons would be affected.
Currently various reproductive options are available to families. The preconception options include MicroSort which is a technology that can separate sperm containing X chromosomes allowing for an increase in chances of having a female. The second reproductive option is preimplantation genetic diagnosis PGD , which is a technique that can allow the cells of a fertilized egg to be tested to determine if it contains a change in the DMD gene and then implant those eggs which do not.
The post conception options include Chorionic Villus Sampling CVS and amniocentesis which analyze sampled cells derived from the developing fetus.
Several of the prenatal testing options for pregnancies at increased risk are available when the DMD disease-causing mutation has been identified in a family member, or if informative, genetically-linked markers have been identified.
Duchenne and Becker muscular dystrophy. Finding Reliable Health Information Online. About Duchenne Muscular Dystrophy. Dystrophin is primarily found in the skeletal muscles, which are responsible for movement, and the in the heart or cardiac muscle. Dystrophin normally functions to strengthen and protect muscles from damage when they contract and relax.
It acts as an anchor , keeping muscle cells together and connecting them with surrounding structures. With little or no functional dystrophin is being produced in muscle cells, these cells are damaged each time muscles contract.
Over time, damaged cells weaken and die and are replaced by scar tissue, leading to muscular weakness. Different types of mutations can be associated with differences in disease severity and may be treated with different types of medication. Some types are discussed here.
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