Dystrophin gene (DMD) exons 45-55 (DMD exons 45-55)

The Dystrophin gene (DMD) exons 45-55 region is a critical therapeutic target for Duchenne Muscular Dystrophy (DMD), a severe X-linked muscle-wasting disease [1, 2]. This specific genomic area is a known "hotspot" for deletions that disrupt the mRNA reading frame, preventing the production of functional dystrophin protein [2]. Dystrophin is essential for maintaining muscle fiber structural integrity by linking the internal cytoskeleton to the extracellular matrix [1]. Without it, muscle fibers undergo progressive degeneration, leading to loss of ambulation and respiratory failure [1, 2]. Therapeutic strategies targeting this region primarily utilize antisense oligonucleotides (ASOs) to induce "exon skipping" during pre-mRNA splicing [7]. By masking specific exons within this range, such as exon 45, 51, or 53, these drugs restore the reading frame and allow for the production of a truncated but partially functional dystrophin protein [3, 4, 6]. This approach aims to convert the severe DMD phenotype into a milder Becker Muscular Dystrophy (BMD) phenotype [7]. Several FDA-approved therapies, including eteplirsen and casimersen, specifically target exons within this 45-55 range to treat patients with amenable mutations [3, 6]. Ongoing research also explores multi-exon skipping of the entire 45-55 region to provide a universal treatment for a larger subset of patients [2, 7]. Monitoring efficacy typically involves measuring dystrophin protein levels in muscle biopsies and assessing motor function through standardized clinical tests [3, 5].

Other names

DMD deletion hotspotDystrophin exons 45-55DMD exons 45 to 55DMD hotspot region

Antisense oligonucleotide-mediated exon skipping to restore the mRNA reading frame, enabling the production of an internally truncated but functional dystrophin protein [3, 7].