What causes Duchenne muscular dystrophy?
Mutations in the dystrophin gene lead to the absence of, or defects in, dystrophin – an important component of the muscle cell membrane.1,2
Dystrophin is an important component of the muscle cell membrane1
Dystrophin is present in all muscles, including skeletal, cardiac and respiratory muscle.2,4,5 Dystrophin is a structural protein that provides mechanical stability5–7
Dystrophin protein structure and interactions
Dystrophin:
- Links internal cytoskeleton to sarcoglycans/dystroglycansin the membrane and the extracellular matrix5,6
- Provides mechanical stability and structure to muscle cell membrane during contraction5–7
- Critical to structure/stability of all muscles, including respiratory and cardiac muscles5
The absence of dystrophin leads to muscle degeneration and fibrosis11,12
Once muscle is lost it cannot be replaced.2,10,12 The absence of dystrophin in Duchenne muscular dystrophy results in ongoing muscle damage, and replacement of muscle fibres by scar tissue and fat12
With permission from H Lee Sweeney, PhD, Myology Institute, University of Florida, FL, USA.
By the age of 5, prominent muscle weakness becomes evident with a 50–60% drop in strength14
By age 6, only 60% of predicted muscle mass is retained, decreasing to just 20% at age 1615
Early intervention is critical to help delay disease progression and treat potentially life-threatening complications.2,8–10
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1. Goemans N, et al. Euro Neuro Rev. 2014;9(1):78–82.
2. Birnkrant DJ, et al. Lancet Neurol. 2018;17:251–267.
3. Marieb EN, Mitchell SJ. Human anatomy & physiology. 9th edition. Pearson; 2013.
4. Muscular Dystrophy Association. DMD muscular dystrophy (DMD): causes/inheritance. Available at: https://www.mda.org/disease/DMD-muscular-dystrophy/causes-inheritance [last accessed November 2020].
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11. Grounds MD, et al. Dis Model Mech. 2020;13(2):dmm043638.
12. Blake DJ, et al. Physiol Rev. 2002;82:291–329.
13. Sweeney HL. Developing skeletal muscle MRI/MRS as a biomarker for DMD therapeutic development. 2014 Annual Connect Conference, Chicago, IL, USA.
14. Mendell JR, Lloyd-Puryear M. Muscle Nerve. 2013;48:21–26.
15. Griffiths RD, Edwards RHT. Arch Dis Child. 1988;63:1256–1258.