Duchenne is a genetic condition. This means the condition is caused by genetic mutations – alterations or changes – in a gene. Duchenne is caused by mutations in a single gene called the dystrophin gene. These mutations prevent cells from producing the dystrophin protein which is needed for muscle function.
What is a deletion mutation?
A deletion occurs when more than one letter is deleted from the DNA code. The dystrophin gene is the biggest in human cells – the DNA code is more than 10,000 letters long and deletions can range in size from just a few letters to many thousands of letters.
Deletions cause approximately 60-70% of cases of Duchenne.
DNA code is always read in triplets – or groups of 3 letters. If the number of letters deleted cannot be divided by 3, then the deletion prevents a cell reading the message correctly. If you imagine a short sentence of 3 letter words:
THE CAT AND DOG RAN AND RAN
and delete 7 letters (for example from the A in cat to O in dog) a cell can no longer read the information.
THE CGR ANA NDR AN
In Duchenne, deletions are often so big that they are described by exon number (for example you might hear “exon 44 deletion”).
The dystrophin gene has 79 exons which must be pieced together for a cell to produce dystrophin protein and any combination of exons could be deleted. This means there are lots of different deletion mutations.
In-frame vs Out-of-Frame
An out-of-frame mutation is one that prevents the gene being read in triplets. These mutations cause Duchenne.
Sometimes a deletion will remove a multiple of 3 letters (for example, 9, 81 or even 3309 letters) from the gene. In this case, the cell is still able to read the code and can produce a dystrophin protein that is smaller than normal but retains some function. This is called an in-frame mutation results in a related condition called Becker muscular dystrophy. Becker muscular dystrophy is usually less severe than Duchenne
Unfortunately no rule is perfect, and sometimes in-frame mutations can cause Duchenne. Often this won’t become apparent until doctors understand how the condition is progressing in an individual.
Which treatments might help?
Everybody living with Duchenne will be offered corticosteroid treatment
In the USA there are exon skipping treatments in the clinic for some people living with Duchenne caused by a deletion mutation. These treatments have not been approved in Europe, but clinical trials are taking place.
There are also trials of other potential therapies taking place and you can find out more about approaches to treating Duchenne caused by deletion mutations on our information pages about:
- Steroid replacements
- Gene therapy
- Exon skipping
Got a question?
If you’ve got a question, we’re happy to help. You can get in touch by emailing Neil (our Head of Research) or call us on 02072508240.
