DMD gene exon 51

The DMD gene exon 51 is a specific coding segment within the largest human gene, the DMD gene on the X chromosome, which spans 79 exons and encodes dystrophin, a cytoskeletal protein essential for maintaining muscle cell membrane integrity during contraction. Mutations in the DMD gene, particularly deletions affecting exons 45-55 including those amenable to exon 51 skipping (about 13% of DMD cases), disrupt the reading frame, leading to absent or nonfunctional dystrophin, progressive skeletal and cardiac muscle degeneration, and Duchenne muscular dystrophy (DMD), an X-linked fatal disorder primarily affecting males. In DMD patients with out-of-frame deletions (e.g., ending at exon 50 or starting at exon 52), therapeutic skipping of exon 51 reframes the mRNA, enabling production of a shorter, partially functional dystrophin akin to that in milder Becker muscular dystrophy (BMD). Eteplirsen (Exondys 51), an antisense oligonucleotide, binds exon 51 of dystrophin pre-mRNA to induce this skipping, received FDA accelerated approval in 2016 based on dystrophin increases, though confirmatory trials for motor benefits are ongoing. Animal models, like DMD exon 52-deleted pigs, show that combined exon 51-52 deletion restores dystrophin, normalizes muscle proteome, reduces fibrosis, and improves cardiac function, supporting the approach. This positions DMD gene exon 51 as a key therapeutic target for mutation-specific DMD gene correction strategies.

Other names

exon 51 of the DMD geneDMD exon 51

exon skipping via antisense oligonucleotide binding to pre-mRNA, restoring the dystrophin reading frame to produce truncated functional dystrophin