What is the genetic cause of Duchenne muscular dystrophy?
Duchenne muscular dystrophy (DMD) is a genetic disorder, which means that it is caused by changes (mutations) in a certain gene.1,2
Genes are made up of DNA, a code that tells the cells in our body how to make proteins. Proteins are the building blocks of our bodies, and they are needed to make and replace cells.
In DMD, there is a mutation in the gene that codes for dystrophin – an important protein that helps to keep muscles working properly.3 As a result, the body cannot make dystrophin.
Without dystrophin, muscle cells are easily damaged.2,4
DMD can be caused by different types of mutations
Most cases of DMD are caused when large pieces of the dystrophin gene are lost or deleted (‘deletions’). Less often, large pieces of the dystrophin gene are copied or duplicated (‘duplications’). DMD can also be caused by smaller changes in the DNA code.4,5
Although most therapeutic strategies can be used regardless of the genetic mutation, in some cases treatment specifically for a particular mutation may be available.5
How do the genetic mutations that cause DMD happen?
The mutation in the gene that codes for dystrophin can be either:6,7
- Passed down through the family (inherited), or
- Caused by a new genetic change – this is called a ‘spontaneous mutation’
Spontaneous mutations mean that sometimes DMD can occur without any family history of the disease. These new mutations can also be passed onto the next generation.6,7
The dystrophin gene is the largest known human gene, which means that it is at more risk of spontaneous mutations than smaller genes.1
These new mutations can arise in a mother’s egg cell in two ways:
- The mutation occurs when the mother’s body makes the egg cell7
If this particular egg cell is fertilised, the baby will carry a faulty dystrophin gene. - The mutation occurs at conception (when the mother becomes pregnant)8
In this case, the baby will carry a faulty dystrophin gene.
When the baby grows up, they can pass the faulty dystrophin gene on to the next generation.6,7
Around two-thirds of DMD cases are caused by an inherited mutation.6 Learn how DMD is inherited
1. Goemans N, et al. Eur Neurol Rev. 2014;9:78–82.
2. Birnkrant DJ, et al. Lancet Neurol. 2018;17:251–267 [Part 1].
3. Ervasti JM. Biochim Biophys Acta. 2007;1772:108–117.
4. Amato AA, Brown RH Jr. Muscular dystrophies and other muscle diseases. In: Longo DL, et al., editors. Harrison’s principles of internal medicine. 19th edition.
5. Kalman L, et al. J Mol Diagn. 2011;13:167–174.
6. Duchenne UK. What are the causes of DMD? Available at https://www.duchenneuk.org/faqs/what-causes-duchenne [last accessed March 2021].
7. Muscular Dystrophy Association. Causes/inheritance. Available at https://www.mda.org/disease/duchenne-muscular-dystrophy/causes-inheritance [last accessed March 2021].
8. National Institutes of Health. What is a gene mutation and how do mutations occur? Available at https://ghr.nlm.nih.gov/primer/mutationsanddisorders/genemutation [last accessed March 2021].