Duchenne Muscular Dystrophy
Amongst the many monogenic disorders that disrupt muscle structure and function, Duchenne Muscular Dystrophy (DMD) is the commonest form of dystrophinopathies. It is a major lethal neuro-muscular disorder that affects 1 in 5000 male live births globally. It exhibits an X-linked recessive pattern and is caused (in 70% of the cases) due to frame-shift deletions and duplications in the X-linked DMD gene. There could also be point mutations that lead to premature termination codons.
The DMD is the largest human gene that codes for Dystrophin which is a cytoskeletal protein. It provides structural stability by acting as a mechanical linker between the associated protein complex (DAPC) and the cytoskeletal gamma (γ)-actin. An absence of Dystrophin leads to the loss of that complex which makes myofibres susceptible to the
The chromosomal locus of DMD i.e. Xp21 is the same for the less severe dystrophinopathy called Becker Muscular Dystrophy (BMD. The latter progresses relatively slowly and is due to mutations resulting in a shorter but partially functional Dystrophin protein.
DMD patients exhibit loss of ambulation loss at a young age, followed by cardiac and respiratory failure soon after,
Recent therapeutic strategies include pharmacological therapy, cell therapy, and gene therapy.