Fig. 1: DMD gene organization and associated protein products.

The full-length dystrophins (Dp427m,c,p) have a modular structure containing the N-terminus (NT) with F-actin binding sites, an extensive central rod domain that consists of β-spectrin-like repeats (oval shape symbols) with binding sites for F-actin, sarcolemma and multiple cellular proteins, and proline-rich hinge regions (H1-H4) predicted to form triple-helical coiled coils, followed by cysteine-rich (CR) and C-terminal (CT) domains. The shorter dystrophin isoforms (Dp260, Dp140, Dp116, Dp71) exhibit at least the cysteine-rich (CR) and C-terminal (CT) domains, except Dp40 that share the Dp71 first exon but misses the CT domain due to an alternative polyadenylation that generates a stop codon. The CR region contains a WW domain, two EF-hands, a β−dystroglycan binding site, and one ZZ domain. The C-terminal region contains two syntrophin binding sites and a coiled-coil domain interacting with dystrobrevins. The light blue rectangular boxes indicate the position of the promoter region of each isoform. The main tissues expressing the distinct dystrophin isoforms are indicated on the right. The figure was Created in BioRender¹⁰¹.