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

The Dystrophin gene (DMD) exons 45–55 region is a critical mutation hotspot located within the central rod domain of the largest known human gene (NIH, 2019). Mutations in this region, particularly out-of-frame deletions, are the primary cause of Duchenne Muscular Dystrophy (DMD), a severe and fatal X-linked muscle-wasting disease (PNAS, 2022). This specific genomic segment is a major therapeutic target because skipping or excising the entire 45–55 block can restore the reading frame for approximately 40–47% of DMD patients, potentially converting a severe DMD phenotype into a much milder Becker Muscular Dystrophy (BMD) phenotype (University of Alberta, 2022). Current therapeutic strategies include antisense oligonucleotides (ASOs) for single-exon skipping, such as eteplirsen and casimersen, and emerging multi-exon skipping cocktails or gene-editing technologies like PBGENE-DMD designed to permanently remove the 45–55 region (Precision BioSciences, 2024). Restoring dystrophin expression through these methods aims to stabilize the sarcolemma and improve muscle function by reconnecting the actin cytoskeleton to the extracellular matrix (Frontiers, 2024). However, significant challenges remain, including the efficient delivery of therapies to cardiac tissue and the potential for clinical variability even among patients with identical in-frame deletions (NIH, 2024).

Other names

DMD mutation hotspotExon 45-55 regionDystrophin exons 45-55del45-55 region

Antisense-mediated exon skipping or CRISPR/ARCUS-mediated gene excision to restore the open reading frame of the DMD gene, allowing for the production of a truncated but functional dystrophin protein.