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A mutation on the gene takes the form of a change to the order of the units within the DNA. A particular section might get cut out, or it might be repeated or it might get jumbled up. Not all these changes have an effect, as they may occur in a passage of DNA which is redundant (there is plenty of this) or the change might not be sufficient to affect the role of the gene.

There are a number of different types of mutation, though the subject is too complex to cover in detail here. The majority of these mutations stop in its tracks the process by which the ATM gene produces ATM protein. These are known as ‘truncating mutations’ and produce no viable protein. These are the mutations that cause classic A-T.

However, there are a number of mutations that are of particular interest in understanding and treating    A-T:

Nonsense mutations

All genes have a particular chemical group, normally towards the end of the gene, which tells the protein-making process to stop. This group is known as a ‘stop-codon’. In a nonsense mutation, a stop-codon is created in the middle of the gene. It’s as if halfway through a recipe, we came to the words “the End”. The result is that the production of the protein stops in the middle, leaving an unfinished protein. This form of mutation is of interest because there appear to be certain drugs that can ‘read across’ this stop-codon and allow the protein to be finished. Researchers, and in particular Richard Gatti, are trying to identify a drug that will do this for ATM.

Splice site mutations

This kind of mutation can in some cases allow a small amount of protein to be made. This is the case with one particular mutation, known as ‘IVS40-1050A>G’, which is particularly common in the population of the UK and Ireland, where it is found in around 10% of people with A-T. This mutation allows perhaps 4% of the normal production of ATM protein. While this is not enough to protect from A-T, it does result in a milder form of the condition.

Missense mutations

A missense mutation involves a small change to a single chemical group. This can sometimes result in the production of a protein which is very similar to the normal form and may function with some of the effect of the normal protein. Where this is the case, again it can result in a milder form of the condition.