Dystrophin gene (DMD) exon 50 splice-region locus (DMD exon 50)

The dystrophin gene (DMD) exon 50 splice-region locus is a critical genomic segment within the DMD gene, which encodes the dystrophin protein essential for maintaining muscle fiber integrity [1.2.2, 1.4.5]. Dystrophin acts as a structural link between the internal cytoskeleton of muscle fibers and the surrounding extracellular matrix [1.4.2, 1.4.5]. Mutations in or around this locus, such as deletions or splice-site mutations, often disrupt the translational reading frame, leading to a complete lack of functional dystrophin and resulting in Duchenne Muscular Dystrophy (DMD) [1.4.1, 1.4.2]. This locus serves as a therapeutic target for antisense oligonucleotides (ASOs) designed to induce "exon skipping" [1.1.3, 1.4.1]. By masking the splice-region of exon 50, these drugs (e.g., NS-050/NCNP-03) cause the cellular splicing machinery to bypass the exon during mRNA processing, thereby restoring the reading frame and allowing for the production of a truncated but partially functional "Becker-like" dystrophin protein [1.2.3, 1.4.1]. This approach aims to slow disease progression and improve muscle function in patients with specific amenable mutations [1.2.3]. Additionally, this locus is a target for experimental gene editing strategies, such as CRISPR/Cas9, which aim to permanently correct splice-site mutations or induce permanent exon skipping [1.4.4]. Therapeutic monitoring involves measuring dystrophin protein levels and the efficiency of exon skipping in muscle biopsies [1.1.5, 1.3.3]. Safety considerations for drugs targeting this locus include potential renal toxicity and infusion-related reactions common to the ASO class [1.1.4, 1.3.5].

Other names

DMD exon 50Dystrophin pre-mRNA exon 50Dystrophin gene exon 50 splice siteDMD exon 50 locus

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