Learn The BasicsDuchenne muscular dystrophy (DMD) is a monogenic disease, which is a disease caused by mutations to a single gene called the DMD gene.
This gene codes for a protein called dystrophin, which is essential for the health and structural integrity of muscle cells.
Mutations in the DMD gene lead to a loss of functional dystrophin protein being made from this gene.
This results in muscle cells becoming damaged at each muscle contraction and wasting away to eventually be replaced by scar tissue.
Different types of mutations in the DMD gene
There are different types of mutations in the DMD gene that can cause the body not to be able to make functional dystrophin protein.
Around 60 to 70% of mutations in the DMD gene are deletions, i.e. portions of the genes missing, whereas 5 to 15% are duplications or a fragment of the gene repeating itself. Around 20% of mutations are so-called point mutations where a single letter in the genetic code is changed, small deletions, or insertions, i.e. few letters being removed or inserted in the genetic code, respectively.
In most cases, the mutations disrupt the reading frame of the gene, or they may introduce a premature stop signal resulting in the protein made from the gene being abnormal and being destroyed by the cells.
Inheritance of DMD
The DMD gene is located on the X chromosome. Because males have only one X chromosome, they will develop DMD if they inherit the X chromosome that has the faulty gene from their mother.
Since females have two X chromosomes, even if they have a mutated DMD gene in one of their X chromosomes, the other healthy copy of the gene is generally able to compensate for the mutation and females typically do not develop the severe symptoms. However, they have a 50% risk of passing it on to their children.
If the child inherits a Y chromosome from the father, he is a male and develops DMD if he inherits an X chromosome carrying the mutated DMD gene from his mother. But if he inherits the X chromosome that has the normal copy of the gene, he will not develop the disease.
If the child inherits the X chromosome from her mother, she is female and may either be a carrier of DMD (in case she inherits the X chromosome carrying the faulty DMD gene from her mother) or not be a carrier (in case she inherits the X chromosome carrying the normal DMD gene from her mother).
In females, one of the two X chromosomes in each cell is randomly “turned off” in a process called X inactivation. In most female DMD carriers, about half of their cells use the healthy DMD gene, allowing them to produce some dystrophin and preventing severe symptoms. However, in some cases, X-inactivation is skewed, meaning that more cells deactivate the healthy X chromosome instead of the one with the mutation. When this happens, the body produces less dystrophin than normal, leading to mild to moderate symptoms in some carriers.
Risk factors associated with DMD
Sex is the strongest risk factor associated with DMD, as the disease almost exclusively affects males, though females are still able to contract it.
DMD occurs in all racial and ethnic groups. However, a 2018 study suggested that the disease is significantly more common in white males than males of other races.