Dp427

Dp427 refers to the full-length dystrophin protein, a key cytoskeletal component encoded by the DMD gene on the X chromosome (location Xp21.2). It has a molecular weight of about 427 kDa and comprises roughly 3,685 amino acids. Dp427 is the principal product in muscle and serves to connect the cytoskeleton to the extracellular matrix, supporting sarcolemma stability during muscle contraction.

Structurally, dystrophin consists of an N-terminal actin-binding domain, a central flexible rod composed of spectrin-like repeats, and a C-terminal domain that binds to the dystrophin-associated protein complex. Through these regions, Dp427 links F-actin to membrane proteins such as dystroglycan and sarcoglycans, anchoring the cytoskeleton to the extracellular matrix and participating in signaling pathways that influence membrane integrity and cell survival.

Dp427 has several tissue-specific isoforms produced by alternative promoters. The best characterized are Dp427m (muscle), Dp427c (brain), and Dp427p (Purkinje cells). Additional shorter isoforms, such as Dp260, Dp140, and Dp71, arise from separate transcriptional start sites. Each isoform shares the core dystrophin domain architecture but differs in tissue distribution and function.

Clinically, mutations in the DMD gene leading to loss or disruption of Dp427 cause Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD), both X-linked disorders. DMD typically presents in early childhood with proximal muscle weakness and cardiomyopathy, while BMD is milder. Diagnosis relies on genetic testing and elevated serum CK levels; muscle biopsy shows dystrophic changes.

Therapeutic approaches include corticosteroids for symptom management, exon-skipping antisense therapies for specific mutations (such as those enabling restoration of the reading frame), and ongoing gene therapy research using micro-dystrophin constructs or genome editing to restore Dp427 function.