DMD

DMD, the largest known human gene, provides instructions for making a protein called dystrophin. There are many different versions of dystrophin, some of which are specific to certain cell types. Dystrophin is located chiefly in muscles used for movement (skeletal muscles) and the muscles of the heart (cardiac muscles). Small amounts of the protein are present in nerve cells in the brain.

In skeletal and cardiac muscles, dystrophin is part of a group of proteins that work together (a protein complex) that strengthens muscle fibers and protects them from injury as muscles contract and relax. The dystrophin complex acts as an anchor, connecting each muscle cell's structural framework (cytoskeleton) with the lattice of proteins and other molecules outside the cell (extracellular matrix). The dystrophin complex may also play a role in cell signaling by interacting with proteins that send and receive chemical signals.

Little is known about the function of dystrophin in nerve cells. Research suggests that the protein is important for the normal structure and function of synapses, which are specialized connections between nerve cells where cell-to-cell communication occurs.

Duchenne and Becker muscular dystrophy - caused by mutations in the DMD gene

Hundreds of mutations in the DMD gene have been identified in people with the Duchenne and Becker forms of muscular dystrophy. Most of these mutations delete part of the DMD gene. Other mutations abnormally duplicate part of the gene or change a small number of DNA building blocks (nucleotides) in the gene.

Mutations that cause Becker muscular dystrophy, which typically has milder features and a later age of onset than Duchenne muscular dystrophy, usually lead to an abnormal version of dystrophin that retains some function. Mutations that cause the more severe Duchenne muscular dystrophy typically prevent any functional dystrophin from being produced.

Skeletal and cardiac muscle cells without enough functional dystrophin become damaged as the muscles repeatedly contract and relax with use. The damaged cells weaken and die over time, causing the characteristic muscle weakness and heart problems seen in Duchenne and Becker muscular dystrophy.

other disorders - caused by mutations in the DMD gene

Mutations in the DMD gene also cause a form of heart disease called X-linked dilated cardiomyopathy. This condition enlarges and weakens the cardiac muscle, preventing it from pumping blood efficiently. Although dilated cardiomyopathy is a sign of Duchenne and Becker muscular dystrophy, the isolated X-linked form of this heart condition is not associated with weakness and wasting of skeletal muscles. Researchers are not certain why some mutations in the DMD gene cause X-linked cardiomyopathy instead of muscular dystrophy. They believe that some DMD mutations affect a version of dystrophin that is specific to heart muscle.