DMD

About DMD

DMD on chromosome Xp21.2 is the largest known human gene, spanning more than 2 million base pairs with 79 exons. It encodes dystrophin, a structural protein linking the actin cytoskeleton of muscle fibers to the extracellular matrix through the dystrophin associated glycoprotein complex, protecting the muscle membrane during contraction. Pathogenic variants cause Duchenne muscular dystrophy, an X linked disorder that affects roughly 1 in 3,500 to 5,000 male births. Frameshifting deletions and other variants that abolish dystrophin production cause Duchenne disease, with progressive weakness beginning in early childhood, loss of walking typically in late childhood or early adolescence, cardiomyopathy, and respiratory failure. In frame variants that allow a shortened, partly functional protein cause the milder Becker muscular dystrophy. The gene was identified in 1986 by Louis Kunkel and colleagues. Corticosteroids are used to slow progression. Exon skipping antisense drugs such as eteplirsen aim to restore the reading frame for patients with specific deletions, and a gene therapy delivering a shortened microdystrophin by AAV vector received accelerated approval in the United States in 2023.