Duchenne Muscular Dystrophy: Forward for Casual Readers

Duchenne Muscular Dystrophy: Forward for Casual Readers

            Duchenne Muscular Dystrophy (DMD) is a genetic disorder of the muscles that causes severe muscle wasting and leads to death at a young age. DMD affects about 1 in every 3500 male births and is much rarer in females. Afflicted are born without symptoms, but muscle weakness first appears around the ages of 3 to 5. Initially, it affects only the distal muscles of the legs and arms, but it rapidly progresses to all muscles in the body. By the age of 12, most patients lose the ability to walk and are wheelchair bound. Death usually occurs before the age of 30 due to weakening of the heart and lungs.

            DMD is caused by a mutation of the DMD gene, which codes for the protein dystrophin.1 It is an inherited X-linked recessive disorder, meaning the mutation causing the disease is a recessive trait located on the X chromosome. The X chromosome is one of two sex-linked chromosomes, the other being the Y chromosome. This is the reason why the disease is so much more common in males; females have the sex chromosomes XX, and so if one of their X chromosomes has the recessive mutation, the other will still work properly (this is known as a female carrier). Thus, they need two mutated X chromosomes to express the disease. Males, who have the sex chromosomes XY, only have one X chromosome. So if that chromosome carries the mutation, there is no other functional one to use.

            About two thirds of DMD patients acquire the disease from inheritance, and the remaining third from spontaneous new mutations. DMD is not caused by the same mutation in everyone. A variety of different mutations can be responsible. What these mutations all have in common is that they are frameshift mutations.2 Genes are expressed by transcribing DNA into mRNA, and then translating the mRNA into proteins made of a chain of amino acids. In this process, DNA is read three nucleotides at a time, corresponding to one amino acid per three bases. Frameshifting mutations are any mutations that change the nucleotide sequence such that this reading frame is thrown off. For example, deleting or inserting a nucleotide at any given spot will change the three-nucleotide code at that spot, while shifting all subsequent nucleotides forward or backward, completely changing the makeup of each three-nucleotide unit and therefore the amino acid that corresponds to that unit. The result is a protein completely unrecognizable from its normal form.

            In DMD patients, this ultimately results in a complete loss of functional dystrophin. Dystrophin is a protein found inside of muscle cells attached to the sarcolemma (muscle cell membrane). Its role is to connect the cytoskeleton, or the interior structural framework of the cell, to the extracellular matrix, a network of structures and molecules outside of and between cells. It does this by binding to a complex of proteins bound to the cell membrane, which themselves are bound to proteins of the extracellular matrix.3 This provides support and stability to the sarcolemma, and helps to orient other important membrane proteins.

            Without dystrophin, the sarcolemma becomes much more fragile, and is prone to tearing. This allows calcium ions from outside the cell to flow into the cell at excessive levels. Calcium ions are used in healthy muscle cells in the process of muscle contraction. At abnormally high levels however, calcium ions serve as activators of multiple processes inside the cell that cause inflammation and cell death.4 The high rates of cell death in DMD patients cause necrosis of muscles, which eventually cannot keep up with regeneration and begin to degrade. Muscle tissue is replaced with fibrous connective tissue and fat that does not contract, which contributes to the muscle weakness/degradation of DMD patients.

            DMD currently has no cure and is universally fatal. Treatment is limited to alleviating symptoms in order to improve patient quality of life and provide small delays in the progression of the disease. However, a number of promising genetic treatments are currently being studied. One such technique, called “exon skipping”, involves removing exons (large sections of DNA that constitute a subunit of the coded protein) that contain a mutation. Removing damaged exons keeps the reading frame intact, allowing for the expression of a shorter, but still functional dystrophin protein. Very recent research is also exploring the possibility of CRISPR/Cas9, a relatively new technique that allows for precise editing of the genome. If successful, such techniques could revolutionize the ability of doctors to prolong the lives of DMD patients in the coming years.

To read further, view these in-depth pages about the history, characterization, pathology, and treatment of the disease.


  1. Hoffman EP, Brown RH Jr. Kunkel LM. 1987. Dystrophin: the protein product of the duchenne muscular dystrophy locus. Cell. 51(6):919-28. DOI: 10.1016/0092-8674(87)90579-4
  2. Monaco et al. 1988. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics. 2(1):90-95. DOI: 10.1016/0888-7543(88)90113-9
  3. Ervasti JM and Campbell KP. 1991. Membrane organization of the dystrophin-glycoprotein complex. Cell. 66(6):1121-1131. DOI: 10.1016/0092-8674(91)90035-W
  4. Burr AR and Molkentin JD. 2015 Genetic evidence in the mouse solidifies the calcium hypothesis of myofiber death in muscular dystrophy. Nature 22(9):1402-1412.

34 comments on “Duchenne Muscular Dystrophy: Forward for Casual Readers

  1. Blog is well written and concise. It uses relevant and detailed sources to provide a strong foundation for this informational article.

  2. DMD was explained in a way that made it easy to understand. I hope the genetic studies can help patients in the future.

  3. Thank you for this easy to read explanation. As a pediatric physical therapist, I have treated children with DMD. This article provided a nice insight into the pathology behind this sad, progressive disease.

    1. Thanks for reading and commenting! It is indeed a sad disease but current genetic treatments are thankfully very promising.

  4. Very informative and easy to understand read on DMD. Hoping that medical advances prove successful in prolonging the lives of those with DMD. Excellent job Ryan!

  5. Nicely summarized. For the rare female DMD patients, are the dystrophin mutations found on the second X chromosome generally random? Do you know how the disease presents in these rare females, particularly regarding severity?

    1. Thanks Auntie Allie! Female DMD patients are indeed the result of a random mutation on the second X chromosome, as it is extremely unlikely that a male with DMD would ever have the chance to have children (which would pass on the mutated X chromosome). In fact, a rare female patient’s mutation helped researchers locate the DMD gene on the X chromosome in the late 80s, by tracking the site of the mutation. The disease would also be just as severe in females, as they also completely lack dystrophin.

  6. Well written. Question – how does the mutation of the DMD gene result in loss of functional dystrophin? Can the body no longer produce enough of the dystrophin protein to bind the cytoskeleton to the extra cellular matrix?

    1. Thank you for asking! The mutation disrupts what’s called the reading frame of the gene, which is pretty much prevents it from being translated from DNA to amino acids (which proteins are made of). DNA is made of four bases, A G T and C. Proteins are coded for by placing together any three of those bases into a single reading unit called a codon. The reading frame is the specific order that they are read in to produce the correct amino acids. For example, the sequence TACTGGCAGAGU is read as TAC TGG CAG AGU, and each of those three letter codons is translated into the amino acids Tyrosine Tryptophan Glutamine and Serine respectively. However, if say, the third letter C were deleted, the sequence would become TATGGCAGAGU. This deletion shifts the entire sequence after it out of the reading frame and back one spot, so that it is now read as TAT GGC AGA GU-. Now, the amino acids that come from this mutated DNA become Tyrosine Glycine Arginine and Valine, completely different from the normal sequence. The amino acid sequence is extremely important in the way a protein properly folds and interacts with other molecules in the body. A frameshift mutation completely changes the amino acid sequence after that spot, creating a protein almost completely unrecognizable from dystrophin that is quickly disposed of by the body, as it is useless.

  7. Thanks for the background on DMD. A longtime friend of mine, his dad and his brother all have MD. It is a sad disease which worsens with time.

    1. Thanks Mr. Carbonetto, sorry to hear that. Current treatments are looking very promising though!

  8. Great post, all of your information was very clearly presented and I learned a lot! One question I do have is in relation to the treatments. What specific treatment options are there and how do they help improve patient quality of life?

    1. Thanks for asking Ashling! Currently, the only widely used treatments are light physical therapy (too intense can hasten symptoms) and corticosteroids (anti-inflammatory/reduce immune system) such as deflazacort and prednisone. These treatments can delay the onset of various symptoms, and prolong a patient’s ability to walk on their own, as well as relatively healthy heart and lung function. These treatments are unfortunately very limited however, and can’t do anything more than delay the progression of the disease for a short time. Current research into new genetic treatments are very exciting though, with the potential to restore dystrophin levels throughout the body by “fixing” the gene. Researchers are currently looking into ways of cutting out large sections of the gene that include the DMD causing mutation. This leaves a shortened gene, but one that can still express functioning dystrophin. The first drug using this approach, eteplirsen, was approved by the FDA in 2016!

  9. I found the summary was laid out well, informative and written so I could understand the subject. Great job.

  10. My cousin had muscular dystrophy and unfortunately passed away from it a few years ago. Didnt know much about the disease so I appreciate the read up, well put together.

  11. Job very well done, Ryan. It is so easy to read and understand, thank you for your efforts to write it this way!

  12. The article is interesting and informative. Some of the technical aspects are a little foreign and I had read them a few times to understand. I think this because of my lack of knowledge of genetics and not a result of a shortcoming this article. I would refer this article to anyone who has questions about this disease.

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