DMD
Dystrophin
Gene Summary
RefSeq / NCBIThis gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]
Clinical Phenotype
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD presents with proximal weakness before age 5, calf pseudohypertrophy, and loss of ambulation by early teens. BMD is milder with later onset.
Molecular Mechanism
Dystrophin anchors the cytoskeleton to the extracellular matrix via the dystrophin-associated protein complex (DAPC). Out-of-frame mutations cause DMD; in-frame mutations cause the milder BMD phenotype. Loss of dystrophin leads to membrane fragility, repeated microinjury, inflammation, and fibrosis.
Clinical Hallmarks & Key Evidence
Gowers' sign (using hands to climb up legs when rising from floor) is a classic clinical finding reflecting proximal lower extremity weakness.
Gowers WR. Pseudo-hypertrophic muscular paralysis. 1879.
The 'reading frame rule': out-of-frame mutations (≈95% of DMD cases) prevent functional dystrophin; in-frame mutations (BMD) allow a truncated but partially functional protein.
Monaco AP et al. Am J Hum Genet. 1988;43(4):487-99.
Exon-skipping therapy (eteplirsen, golodirsen) and gene therapy (delandistrogene moxeparvovec, FDA 2023) restore partial dystrophin expression by converting an out-of-frame to an in-frame transcript.
Mendell JR et al. N Engl J Med. 2023;388:2509-2521.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.