Duchenne Muscular Dystrophy (DMD)

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• Duchenne Muscular Dystrophy (DMD)
• Duchenne muscular dystrophy is the most common
  and usually most severe form of muscular
  dystrophy. It is named after Dr Duchenne de
  Boulogne a mid-nineteenth-century French
  physician, who was one of the first people to
  study and document some of the muscular
  dystrophies.

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• Duchenne muscular dystrophy is an X-linked
  recessive muscle-wasting disorder that affects
  about 1 of every 3500 males born.

Inheritance pattern of Duchenne muscular
dystrophy (DMD). Sons have a 50-50 chance of
inheriting the disorder from their mother if she
carries the gene for it on one of her X
chromosomes.
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• A defective gene on the X chromosome (at Xp21
  site) leads to a deficiency in dystrophin
• a rod-shaped cytoskeletal protein which
  normally maintains the integrity of the muscle
  cell wall. Where dystrophin is defi cient, there
  is an influx of calcium ions, a breakdown of the
  calcium calmodulin ????complex and an excess of
  free radicals. These changes lead eventually to
  irreversible destruction of the muscle cells.

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• Dystrophin is a Muscle Protein Identified by
  Study of a Genetic Disease
• Many individuals with DMD have deletions in this
  locus segments of the X-chromosome DNA missing
  in such patients were used to isolate the cDNA
  for the protein missing in DMD. Subsequent
  cloning of this cDNA led to the discovery of
  dystrophin, which is localized to the plasma
  membrane of striated muscle cells and is missing
  in muscles from DMD patients.Dystrophin has a
  molecular weight of 400,000 and constitutes only
  about 0.002 percent of the total muscle protein,
  Although the molecular function of dystrophin is
  not known, it has sequence homology to a-actinin
  and other actin-binding proteins and may be
  involved in anchoring actin filaments to the
  plasma membrane.Clearly it is important in
  preventing degeneration of muscle fibers. The
  identification of dystrophin is an outstanding
  example of reverse geneticsidentifying the
  gene for a protein whose absence causes a genetic
  disease even when the function of the protein is
  not known.

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Structure of a muscle. In the Duchenne muscular
dystrophy, the attachment of muscle fibers to
their surrounding endomysium (extracellular
matrix) becomes weakened due to mutations in the
dystrophin gene.
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