Dystrophin (DMD) gene (DMD)

The Dystrophin (DMD) gene, located on the X chromosome, is the largest known human gene and encodes a critical cytoskeletal protein essential for maintaining the structural integrity of muscle fibers (NIH, 2023; UniProt, 2024). Dystrophin acts as a molecular shock absorber, linking the internal actin cytoskeleton of a muscle cell to the surrounding extracellular matrix via the dystrophin-associated glycoprotein complex (DAGC) (PubMed, 2002). Mutations in the DMD gene that result in a complete loss of functional protein lead to Duchenne Muscular Dystrophy (DMD), a severe and progressive muscle-wasting disease characterized by myonecrosis, loss of ambulation, and premature death from respiratory or cardiac failure (NIH, 2023). Because the full-length DMD gene is too large to be packaged into standard viral delivery vectors like adeno-associated virus (AAV), therapeutic approaches utilize 'microdystrophin'—a synthetic, highly truncated version of the gene that retains the most critical functional domains (Parent Project MD, 2023). Gene therapies such as delandistrogene moxeparvovec deliver this microdystrophin transgene to skeletal and cardiac muscle cells to restore a functional protein bridge, thereby stabilizing the sarcolemma and slowing disease progression (FDA, 2023; MDA, 2023).

Other names

DMD geneDuchenne muscular dystrophy genemicrodystrophinDMD locusmicrodystrophin gene locus

Gene replacement therapy using adeno-associated virus (AAV) vectors to deliver a truncated, functional version of the dystrophin gene (microdystrophin) to muscle cells to restore protein expression and stabilize the sarcolemma (NIH, 2023; Parent Project MD, 2023).