What is the role of genetics and dystrophin in the etiology of muscular dystrophy?

Updated: Aug 17, 2020
  • Author: Twee T Do, MD; Chief Editor: Jeffrey D Thomson, MD  more...
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In the X-linked forms of MD, such as the Duchenne and Becker dystrophies, the defect is located on the short arm of the X chromosome. [9] Hoffman and coworkers identified the locus of the defect in the Xp21 region, which includes approximately 2 million base pairs. [5] The gene codes for Dp427, which is a component of the cytoskeleton of the cell membrane.

Dystrophin is distributed not only in skeletal muscle but also in smooth and cardiac muscles and in the brain. The large size of the dystrophin gene explains the ease at which spontaneous new mutations can occur, as in Duchenne MD. The large size also allows mistakes in protein synthesis to occur at multiple sites.

Defects that interfere with the translation reading frame or with the promoter sequence that initiates synthesis of dystrophin lead to an unstable, ineffective protein, as in Duchenne MD. Disruption of the translation process further down the sequence leads to production of proteins of lower molecular weight that, although present, are less active and result in the milder variety of Becker MD.

Like Duchenne MD, Emery-Dreifuss MD is a sex-linked recessive disorder, but its defect is localized to the long arm of the X chromosome at the q28 locus. [10] Some authors, however, have cited case reports of similar findings in Emery-Dreifuss that were transmitted in an autosomal dominant pattern. [11] However, this finding is more of an aberration than a normal observation in Emery-Dreifuss MD.

In autosomal recessive conditions such as limb-girdle MD, the genetic defect is localized to the 13q12 locus.

In the autosomal dominant facioscapulohumeral MD, the defect is at the 4q35 locus. In distal MD, it is at the 2q12-14 loci. [12]

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