Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness. It primarily affects males, with an estimated incidence of 1 in every 3,500 to 5,000 male births. DMD is caused by mutations in the dystrophin gene, which is responsible for producing a protein called dystrophin. This protein plays a crucial role in maintaining the structural integrity of muscle fibers.
Genetic mutations: The most common cause of DMD is a mutation in the dystrophin gene located on the X chromosome. This gene provides instructions for the production of dystrophin, a protein that helps strengthen and protect muscle fibers. Mutations in the dystrophin gene lead to the production of an abnormal or nonfunctional dystrophin protein, resulting in muscle weakness and degeneration.
X-linked recessive inheritance: DMD follows an X-linked recessive inheritance pattern. This means that the mutated gene is located on the X chromosome, one of the two sex chromosomes. Males have one X and one Y chromosome, while females have two X chromosomes. As a result, males are more commonly affected by DMD, as they only need to inherit one mutated copy of the dystrophin gene to develop the disorder. Females, on the other hand, need to inherit two mutated copies of the gene to be affected, which is relatively rare.
De novo mutations: In some cases, DMD can occur due to de novo mutations, which are genetic changes that arise spontaneously in the affected individual and are not inherited from their parents. These mutations can occur during the formation of sperm or egg cells or early in embryonic development. De novo mutations in the dystrophin gene can lead to the development of DMD in individuals with no family history of the disorder.
Gene deletion, duplication, or point mutations: The mutations in the dystrophin gene that cause DMD can take different forms. The most common type of mutation is a deletion, where a section of the gene is missing. Duplications, where an extra copy of the gene is present, can also occur. Point mutations, which involve changes in a single nucleotide base, are another type of mutation that can lead to DMD. The specific location and type of mutation can influence the severity of the disorder.
Impact on dystrophin protein: Dystrophin is an essential protein for maintaining the structural integrity of muscle fibers. It helps anchor muscle fibers to the surrounding connective tissue, providing stability during muscle contraction and relaxation. In individuals with DMD, the absence or dysfunction of dystrophin leads to increased susceptibility of muscle fibers to damage and degeneration. Over time, this progressive muscle degeneration results in the characteristic symptoms of DMD.
Secondary factors: While the primary cause of DMD is genetic, there are secondary factors that can influence the progression and severity of the disorder. These factors include inflammation, oxidative stress, and impaired muscle regeneration. Inflammation in the muscle tissue can further damage muscle fibers and exacerbate the symptoms of DMD. Oxidative stress, which occurs when there is an imbalance between the production of reactive oxygen species and the body's ability to neutralize them, can also contribute to muscle degeneration. Additionally, impaired muscle regeneration, often due to the absence of dystrophin, hinders the repair and replacement of damaged muscle fibers.
In conclusion, Duchenne muscular dystrophy is primarily caused by mutations in the dystrophin gene, leading to the absence or dysfunction of the dystrophin protein. These mutations can occur spontaneously or be inherited in an X-linked recessive manner. The specific type and location of the mutation can influence the severity of the disorder. Secondary factors such as inflammation, oxidative stress, and impaired muscle regeneration also contribute to the progression of DMD. Ongoing research aims to develop treatments that address the underlying genetic cause and alleviate the symptoms of this debilitating disorder.