Decoding Dystrophin Gene Mutations: Unraveling the Mysteries of Muscular Dystrophy

Muscular dystrophies are a group of human monogenic disorders causing muscle weaknesses and affecting mobility. Mutations in different genes cause different types including Duchenne, Becker, congenital, Emery–Dreifuss, oculopharyngeal, facioscapulohumeral, myotonic, and limb-girdle muscular dystrophy. Dystrophin gene mutation causes dystrophinopathy, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and DMD-associated dilated cardiomyopathy (DCM), and together these account for approximately 50% of all muscular dystrophies. Dystrophin, the largest known gene in humans is located in chromosome Xp21, spans approximately 2.4 Mb and constitutes 0.08% of the genome. Dystrophinopathy, mainly affecting males with an incidence rate of 1/3500, is characterized by progressive muscle weakness and cardiomyopathy. Initially, weakness emerges in the hips and upper leg muscles around the age of 4, but it can extend to involve the heart, gastrointestinal tract, and respiratory muscles later in the disease course, and the weakness intensifies with time. Although the severity and survival time might vary for DMD, BMD, and DCM, dystrophinopathy has no cure except for the recent gene-therapy approach. Strategies and the potential of innovative therapeutic approaches for DMD have been discussed.