Dystrophin (DMD) genomic DNA sequence (DMD)

The Dystrophin (DMD) genomic DNA sequence is the largest gene in the human genome, located on the X chromosome at locus Xp21.2-p21.1 (NCBI Gene ID: 1756). It encodes the dystrophin protein, which is essential for maintaining the structural stability of myofibers during muscle contraction by linking the intracellular actin cytoskeleton to the extracellular matrix (UniProt P11532). Mutations within this genomic sequence, such as deletions, duplications, or point mutations, disrupt the reading frame and lead to the absence of functional protein, resulting in Duchenne muscular dystrophy (DMD). The "intended duplication/mutation locus" refers to the specific site of genetic error targeted by precision therapies like CRISPR/Cas9 or antisense oligonucleotides (ASOs). Drugs such as Eteplirsen and Golodirsen target the pre-mRNA transcribed from this locus to induce exon skipping, thereby restoring a functional reading frame (FDA). Emerging gene-editing technologies aim to directly modify the genomic DNA at the mutation site to permanently correct duplications or deletions (PubMed: 26720505). These therapies are designed to convert a severe DMD phenotype into a milder Becker muscular dystrophy (BMD) phenotype by producing a truncated but functional protein. Safety considerations include potential off-target effects of gene editing and immune reactions to viral delivery vectors or the newly synthesized protein.

Other names

DMD geneDystrophin geneDMD locusDystrophin genomic sequence

Restoration of the dystrophin protein reading frame through exon skipping, gene replacement, or direct genomic editing at the mutation site.