Types & mutations

Types & Mutations

Duchenne and Becker are caused by mutations (changes) within the dystrophin gene. A gene is made up of coding regions called exons, and the areas between exons are called introns. Making the dystrophin protein involves several steps. The first step is to remove the introns and fitting the exons together, 1 to 79, like puzzle pieces. If there is a missing (deletion) or extra (duplication) piece, the body can have difficulties making dystrophin.Since the dystrophin gene is one of the largest genes in the body, it can have thousands of changes – or mutations that result in Duchenne or Becker. As some new therapies may only treat certain Duchenne and Becker mutations, it will be important to know which mutation the patient has.

The following table from PPMD USA shows the different types of mutations that can happen in the dystrophin gene, and how commonly the different mutations occur in people with Duchenne and Becker.

Type of mutation How often mutation causes Duchenne How often mutation causes Becker
Large deletions 60-70% of all cases 80-85% of all cases
Large duplications 10% of all cases 5-10% of all cases
Point mutations and other small changes (including ‘nonsense’ mutations) 15-30% of all cases 10-15% of all cases

Deletions

Deletions occur when pieces of the gene, called exons, are missing. In most cases, one or more exons missing are the most common type of mutation. There are 79 exons in the dystrophin gene, so there are many deletions that can happen. Certain areas are more likely to have a deletion and are so-called ‘hot-spots’. Exons 44-55 are hot spot regions. If you know the mutation is a deletion, the Exon Deletion Tool can help understand which exons need to be skipped to restore the reading frame, which means the body can make the protein again (albeit a slightly shorter version).

Duplications happen when one or more exons are doubled. This type of mutation is not as common as deletions. Point mutations are smaller changes that do not occur in the entire exon.

Sometimes, just one letter in the DNA code is missing, doubled, or changed. One of the most common point mutations is called a nonsense mutation. This is a premature stop in the gene that stops or hinders the production of the dystrophin protein.

In-Frame or Out-of-Frame deletions

With in-frame mutations, the protein may be shorter than normal, but still functioning. In-frame deletions typically result in Becker because there is some dystrophin present in the cells. In out-of-frame deletions, the reading frame is completely disrupted. In this case, no dystrophin at all is made. This type of deletion is often the case in Duchenne muscular dystrophy.

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