Dystrophin is encoded by the largest gene in the human genome, taking up 0.08%. A deletion of at least one exon is characteristic of around 65% of Duchenne muscular dystrophy (DMD) sufferers and 80% of Becker muscular dystrophy (BMD) patients. Dystrophin is part of the dystrophin complex to stabilise a connection between striated muscle fibres and the plasma membrane. Mutations leading to loss of structure correlate to loss of function and clinical outcome. Loss of dystrophin function leads to instability in the cytoskeleton and the connection of the muscle fibres. This is seen as progressive muscle weakness and wasting in muscular dystrophy diseases. Symptoms can vary, including respiratory failure, irregular heart rhythms, and heart failure.
Understanding the most critical regions of dystrophin for its interaction within the complex and stabilisation of muscle fibres has helped generate therapies to restore dystrophin function in vivo. Viral vectors and exon skipping are current approaches to improve dystrophin levels for muscular dystrophy patients. However, the efficacy of available therapies is highly variable, highlighting the need for further research into dystrophin as a general cytoskeleton regulator within the dystrophin complex.
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