Question

Approximately 15% of disease-causing mutations involve errors in alternative splicing. However, there is a case where an exon deletion enhances dystrophin production in muscle cells of DMD (Duchenne muscular dystrophy) patients. A deletion of exon 45 is the most frequent DMD-causing mutation. But some individuals with Becker muscular dystrophy (BMD), a milder form of muscular dystrophy, have deletions in exons 45 and 46. Given that deletions often cause frameshift mutations, provide a possible explanation for the enhanced production of dystrophin in the presence of exon 45 and 46 deletions.

Answer 1

In case of DMD, the deletion of exon 45 may cause formation of protein that is non-functional. In other words, there is formation of a protein that is structurally (and functionally because protein function depends upon its 3D structure) different from dystrophin because of change in pattern of protein folding.

In case of BMD, it may cause formation of a protein that is upto some extent structurally similar to dystrophin as compared to DMD. The reason is the same i.e. change in folding pattern: The deletion of an extra exon may again cause change in protein folding pattern that may give rise to a protein, which is more structurally similar to dystrophin.