Duchenne Muscular Dystrophy (DMD) is a rare single gene disorder affecting 1 in 3,500 boys. The muscles of the affected person weaken and waste away (atrophy), usually beginning in the lower limbs and then spreading to the upper body as the disease progresses (1). This disorder is caused by recessive mutations in a gene called dystrophin. The dystrophin gene is located on the X chromosome (Xp21.2). Because the X-linked disorder is recessive it occurs mostly in males because males who inherit the mutated chromosome from their carrier mother do not have another copy of the X chromosome to negate it. Symptoms can be first noticed at a very young age when the affected individual is slower to start sitting, standing and walking independently than other children of their age (2). However usually the disease is not recognised until around 6 years of age. There is a continuous decline in muscle strength
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There are several isoforms of this protein but the one found predominantly in muscle is the 427kDa isoform. Dystrophin is made up of four domains: an N-terminal, a rod domain composed of 24 triple helix repeats and 4 hinges, a cysteine-rich domain and a C-terminal. The N-terminal of the protein binds to actin filaments and acts as a bridge between the actin cytoskeleton and the extracellular matrix via interactions with the dystroglycan complex (DGC) in the sarcolemma in muscles (5). Dystrophin helps to increase membrane stability and prevent the sarcolemma from rupturing. Absence of dystrophin leads to the disassembly of the DGC leaving the sarcolemma vulnerable to damage when muscles contract (6). Skeletal and cardiac muscle cells that lack, or have an insufficient amount of, functional dystrophin progressively become more damaged as the muscles keep contracting and relaxing. Damaged muscle cells weaken and eventually die, which is what causes the muscle weakness and cardiomyopathy seen in DMD
There are several isoforms of this protein but the one found predominantly in muscle is the 427kDa isoform. Dystrophin is made up of four domains: an N-terminal, a rod domain composed of 24 triple helix repeats and 4 hinges, a cysteine-rich domain and a C-terminal. The N-terminal of the protein binds to actin filaments and acts as a bridge between the actin cytoskeleton and the extracellular matrix via interactions with the dystroglycan complex (DGC) in the sarcolemma in muscles (5). Dystrophin helps to increase membrane stability and prevent the sarcolemma from rupturing. Absence of dystrophin leads to the disassembly of the DGC leaving the sarcolemma vulnerable to damage when muscles contract (6). Skeletal and cardiac muscle cells that lack, or have an insufficient amount of, functional dystrophin progressively become more damaged as the muscles keep contracting and relaxing. Damaged muscle cells weaken and eventually die, which is what causes the muscle weakness and cardiomyopathy seen in DMD