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 nonsense mutation?
Genes are the instructions that allow a cell to make a protein and the dystrophin gene is the biggest in human cells – the DNA code is more than 10,000 letters long.
A nonsense mutation is a special type of point mutation where a single letter is changed that stops the gene being read.
Point mutations cause 10-15% of cases of Duchenne.
DNA code is always read in triplets – or groups of 3 letters. Just like a computer code, genes have a clearly defined start and finish site that tell a cell where to start reading the instructions and where to stop. If you imagine a short sentence of 3 letter words with a clearly defined start and end:
RUN THE CAT AND DOG RAN AND RAN END
and change a single letter (for example the A in AND)
RUN THE CAT END DOG RAN AND RAN END
There is now a signal (the word END) in the middle of the sentence that tells a cell to stop reading. Although the rest of the message still exists, it cannot be used because the cell stops reading the instructions when it finds the word END.
The technical term for this is a premature stop codon or premature termination codon.
Which treatments might help?
In Europe, Translarna is approved and (in the UK) available on the NHS for Duchenne caused by a nonsense mutation. The drug targets the underlying genetic cause of the condition by helping cells ignore the stop signal in the middle of the dystrophin gene. You can find out more here.
Everybody living with Duchenne will be offered corticosteroid treatment and there are potential treatments designed to work regardless of mutation type being tested in clinical trials. You can find out more about approaches to treating Duchenne caused by nonsense mutations on our information pages about:
- Steroid replacements
- Gene therapy
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.
