Genetic testing for Duchenne muscular dystrophy (DMD) isn’t just used to confirm the diagnosis — it can also provide critical information for treatment and prognosis.
As the largest known human gene, thousands of different mutations have been identified in the DMD gene to date. Understanding which variant you or your child has will help you better navigate the disease and available treatment options.
Why does mutation type matter?
The type of genetic variant a person has can impact which therapies they are eligible for and how quickly their symptoms may progress.
Implications for treatment
Exon-skipping therapies are a type of drug that can only be given to patients with DMD if their specific mutation can be addressed by the therapy. These drugs work by telling the cells to skip over certain parts of the DMD gene when creating dystrophin protein. This way, a functional version of the protein is still formed, although it will be smaller than full-length dystrophin.
Several exon-skipping therapies have been approved for DMD. These include:
- Golodirsen, which skips the 53rd exon of the DMD gene.
- Vitolaresen, which also skips exon 53.
- Eteplirsen, which skips exon 51.
- Casimirsen, which skips exon 45.
Up to 30% of patients could benefit from these four drugs.
Exon-skipping therapies don’t cure DMD, but they have the potential to slow down disease progression. However, much more research is needed to understand their long-term effects.
Implications for prognosis
The current evidence suggests that a patient’s mutation could predict disease severity, although the association isn’t always so clear.
Individuals who have a deletion in exons 3 to 7, or those with deletions around exon 44, tend to have milder symptoms. On the other hand, people with mutations bordering exons 51 and 53 may have a more severe prognosis.
Yet DMD mutations aren’t the only, or even the best, predictor of a patient’s prognosis or life expectancy. Prognosis can be influenced by a variety of factors including the age of treatment initiation and treatment duration.
Read more about DMD prognosis
Modifier genes also play a role
Modifier genes are genes other than the DMD gene that can be mutated in people with DMD and contribute to inflammation and muscle weakness. Among these are SPP1, LTBP4, CD40, ACTN3, TCTEX1D1 and THBS1.
Studies have shown that patients with mutations in modifier genes may have more severe symptoms and may respond differently to certain treatments. For example, some patients with SPP1 mutations may have decreased responses to glucocorticoids, a commonly used drug in patients with DMD.
Currently, screening for modifier gene mutations isn’t standard practice for DMD. However, as more evidence mounts, these genes may emerge as a key factor when it comes to disease management.
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