Dystrophin (DMD) exon 51 splice-donor site (DMD exon 51 SD)

The DMD exon 51 splice-donor site is a specific genomic and pre-mRNA sequence within the dystrophin (DMD) gene that plays a pivotal role in the processing of the dystrophin transcript (Aartsma-Rus & van Ommen, 2007). In patients with Duchenne muscular dystrophy (DMD) who have deletions that disrupt the reading frame (most commonly deletions of exons 45-50 or 48-50), targeting this site allows for the exclusion of exon 51 during splicing. This process, known as exon skipping, restores the open reading frame of the mRNA, enabling the production of a truncated but partially functional dystrophin protein (Mendell et al., 2013). The primary therapeutic agent for this target is eteplirsen, an antisense oligonucleotide that binds to the pre-mRNA to sterically hinder the spliceosome (FDA, 2016). By converting a severe DMD mutation into an in-frame mutation similar to those seen in Becker muscular dystrophy, this approach aims to slow the progressive muscle wasting characteristic of the disease. This target is relevant for approximately 13% of the total DMD patient population. Safety monitoring for drugs hitting this target includes checking for hypersensitivity and potential renal effects.

Other names

DMD exon 51Dystrophin gene exon 51Exon 51 of the DMD geneDMD exon 51 splice site

Antisense oligonucleotide-mediated exon skipping to restore the mRNA reading frame.