Characterizing Mutations to the Dystrophin Gene

Several different types of mutations can affect the dystrophin gene, including large deletions and duplications of one or more exons and small mutations. The terminology used to describe dystrophin mutations is evolving as improvements in testing methodologies allow better characterization of mutations.

During this learning phase, researchers and clinicians may cite different terminology and mutation frequencies. For our use, we characterize dystrophin mutations for Duchenne muscular dystrophy as follows:

  • About 60-70% of cases of Duchenne muscular dystrophy are caused by relatively large deletions of one or more exons.
  • Large duplications of one or more exons account for about 10% of Duchenne cases.
  • Approximately 15-30% of Duchenne cases are the result of small point mutations.

In Becker muscular dystrophy, about

  • 80% of cases are caused by large deletions,
  • 5% by large duplications, and
  • 10-15% by small point mutations.
    • Small point mutations include:
      • Nonsense mutations that create early stop signals to the gene,
      • Splice site mutations that may alter the reading frame of the gene,
      • Small insertions or deletions of a few DNA bases that may or may not alter the reading frame, and
      • Missense mutations, which are rare changes that may compromise the gene function.

Establishing the specific mutation usually allows the lab to determine disruptions to the reading frame of the gene.

  • DNA mutations that result in some protein function are consistent with Becker muscular dystrophy. Such mutations are usually “in frame” mutations, which disrupt the protein but still allow for partial protein production.
  • Mutations that result in completely absent or minimal dystrophin protein (less than 3-5%) are consistent with Duchenne muscular dystrophy. Such mutations are usually “out of frame” or “frameshift” and prevent the creation of a protein product.

Unfortunately, differentiating Duchenne mutations from Becker mutations is not always clear cut, because there are known exceptions to the “in-frame” association with Becker and “out of frame” association with Duchenne. Depending on the site of the deletion, sometimes there is limited ability for the lab to differentiate between the two disorders.