Mild-variant A-T

Although it has been known for some time that in some people with A-T the symptoms appear later and develop more slowly, it is only recently that this has come to be considered as a variant form of A-T. There is not even full agreement over a name for this form of A-T though it is often referred to as Mild-Variant A-T, or Mild A-T. However, this is not a very appropriate name since the symptoms are ultimately the same as for classic A-T and it can only  be considered 'mild' by comparison.

How many people have mild-variant A-T?

In the United Kindom, around one in three cases of A-T are mild variant. This is higher than in many parts of the world due to the fact that one specific mutation which gives a milder form of the condition is relatively common in the United Kingdom and Ireland. This mutation, known as IVS40-1050A>G, appears to have originated in the British Isles. It is present in approximately one in seven of all people with AT.

Because populations vary and other individual populations may have their own genes which are more or less common, it is impossible to say  with any accuracy how many people in other countries may have mild-variant A-T. The UK and Ireland are unusual in that the specific mutations have been identified for almost everyone known to have A-T. Nevertheless, if you discount the effect of the IVS40 gene, the UK population would suggest that a good starting estimate for mild variant A-T in other relatively mixed populations would be around 20% or one case  in five.

Symptoms

The symptoms of mild-variant A-T, are broadly the same as those of classic A-T, except that they tend to progress more slowly and may also appear later. While some people with this form of A-T are diagnosed in childhood, others receive a diagnosis as adults. For some, the symptoms may have been apparent for a while, perhaps appearing during teenage years, but have been misdiagnosed as another condition. For others, they only reveal themselves in adulthood. This great variety in the ways that individuals experience  the condition is typical of A-T.

When the symptoms do develop, they tend to be the same as for those people with classic A-T, both in terms of the neurological and immunolgical problems. However, this form of A-T is rarer than classic A-T and there is much that we still don't know about it.

What causes it?

People with A-T have 2 mutations on the ATM gene, one from each parent. Most A-T mutations are 'truncating mutations', which means they do not allow for the production of any functional ATM protein. However there are a very few mutations that do permit either the production of a small amount of functioning ATM or else the production of a form of 'mutant ATM', i.e. incorrectly--produced ATM, which nevertheless does have some effectiveness.

This connection between certain genes and a milder form of A-T has been found through the excellent work of Prof Malcolm Taylor and his team at Birmingham University, who have sequenced the genes for nearly all people with A-T in the United Kingdom.

Their work has identified a particular mutation, of a type called a 'splice mutation', which has the unwieldy name of ATM5762ins137. This mutation appears to permit around 4% of the normal amount of active ATM to be produced.  The team have also shown that people with A-T who have this mutation have a form of A-T with a later onset and a slower progression than in those patients with two truncating mutations. This particular mutation appears to have arisen in the British Isles and Ireland, where it is estimated that it is found in 10% of people with A-T. It is for this reason that there are more cases of mild-variant A-T found here than in other parts of the world.

There are also a small number of mutations from another category, known as missense mutations, which create mutant protein with some resisdual activitity, which have also been shown to correspond to people with later and slower onset of the condition.

Diagnosis

If you are diagnosed with A-T in the United Kingdom, diagnosis will be confirmed at Professor Taylor's laboratory and the specific mutations will  be identified (very occasionally there is a problem doing this). Normally, if the individual has a mutation which is known to allow some ATM activity you will be told at the time of diagnosis. However, as is made clear repeatedly in this website, A-T is a condition which varies considerably from individual to individual and it is not possible to draw firm conclusions about how it will progress for any one person.

Living with mild-variant A-T

As with all forms of A-T there is great variation in how individuals are affected. Some may be diagnosed as children, while others may not be diagnosed until well into adult life. The degree and nature of any disabilities along with differences in personal circumstances and character make it impossible to generalise about the impact of A-T on people's lives.

Those who are diagnosed later have often lived almost unaffected lives up to that point. Some have children and while most will have had them not knowing that they had A-T there is at least one case of a young woman with A-T having a baby in the full knowledge of her condition.

Those who are diagnosed younger will tend to grow up living with some degree of disability. Fewer of these people work regularly after leaving education, but quite a few become involved in voluntary or artistic activities.

The A-T Society in partnership with the Social Policy Unit of the University of York is currently carrying out a project to talk to young adults living with A-T about their lives so we will be publishing more information on this later in 2012.

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