Exon 51 of the human dystrophin pre-messenger RNA (DMD Exon 51)

The Exon 51 region of the human dystrophin (DMD) pre-messenger RNA is a specific molecular target for antisense oligonucleotide (ASO) therapies designed to treat Duchenne muscular dystrophy (DMD). DMD is a severe X-linked recessive neuromuscular disorder characterized by progressive muscle degeneration due to the absence of functional dystrophin protein, which normally stabilizes the sarcolemma during muscle contraction (Lim et al., 2017). Mutations in the DMD gene, particularly deletions, often disrupt the mRNA reading frame, leading to premature translation termination and a lack of functional protein. By binding to specific sequences within or adjacent to exon 51, ASOs like eteplirsen sterically block the splicing machinery, causing the exclusion of exon 51 from the mature mRNA transcript (FDA, 2016). This 'exon skipping' strategy restores the reading frame, enabling the synthesis of an internally deleted but partially functional dystrophin protein, similar to the truncated protein found in the milder Becker muscular dystrophy (Aartsma-Rus & Corey, 2020). This therapeutic approach is applicable to approximately 13% of the DMD patient population whose mutations are amenable to exon 51 skipping.

Other names

DMD exon 51Dystrophin exon 51Exon 51 of the DMD geneDMD pre-mRNA exon 51

Antisense oligonucleotide-mediated exon skipping by sterically blocking splicing machinery at the exon 51 locus