Scientists discover gene for Huntington's chorea: Ten years' research brings hope of accurate test

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The Independent Online
SCIENTISTS have discovered the gene for Huntington's disease, an inherited disorder of the nervous system that afflicts more than 3,000 people in the UK. The discovery marks the culmination of 10 years' work and raises difficult ethical dilemmas about genetic testing.

Knowing the gene for this fatal and incurable condition, which usually strikes in mid-life, should quickly lead to a 100 per cent accurate test for all people who are at risk.

Researchers are also confident that now they know the fundamental cause of the disease they will learn more about the biological mechanism that results in the death of nerve cells in Huntington's patients.

The scientists believe the discovery will ultimately lead to better treatment of the disease and even, possibly, a cure, although they emphasised they still have a long way to go.

Details of the discovery, by a team of British and American scientists from six research centres, will be published this Friday in the scientific journal Cell.

Huntington's chorea results from a defective gene inherited from one parent. The first symptoms, which occur usually after the age of 35, are intellectual impairment and psychiatric disturbances. Progressive mental and physical deterioration leads to death about 10 or 20 years later.

Because of the delayed 'time bomb' nature of the disease, there are many thousands of relatives of Huntington's patients who are well but at risk of developing the condition.

Many at-risk families have been offered a test developed nearly 10 years ago that is not completely accurate. Most have refused.

This rudimentary test was developed after scientists from the Massachusetts General Hospital, Boston, identified the rough position of the gene on chromosome 4, in 1983.

They have since worked with other research teams to find the gene itself - the longest gene search since the development of the new genetic technology.

James Gusella, head of the Massachusetts team, said scientific co-operation was crucial to the discovery: 'This was a very, very hard mystery to solve. If the separate research teams had been competing rather than cooperating the search could have gone on for a lot longer.'

The two British groups involved were the Imperial Cancer Research Fund, in London, and the Institute of Medical Genetics, at the University of Wales College of Medicine, in Cardiff.

By analysing genetic material taken from more than 100 people in 75 families with a history of Huntington's, the researchers found a mutation in patients with the disease. The mutation is a repetition of the chemical building blocks that make up a DNA molecule; the molecular equivalent of a stutter in the genetic blueprint.

In normal people the 'stutter' is repeated between 11 and 34 times; in Huntington's patients it is repeated between 42 and 86 times, the researchers found. Understanding why the repetition lead to brain degeneration is likely to be the key to a possible cure, they said.

The gene itself is responsible for a protein found in the brain which is unlike any other known protein of the body, Marcy MacDonald, one of the Massachusetts researchers, said. 'Finding this gene is like opening a door into a room we've never seen before. The next step is to learn more about how this protein functions normally and how this is disrupted in Huntington's disease.'

Peter Harper, professor of medical genetics at the University of Wales College of Medicine, said that although the discovery will lead to an accurate test, it should be used with utmost caution. 'It is vital that no pressure is put on people to have tests,' he said.

Professor Harper is particularly concerned about the prospect of pressure for testing from third parties such as insurance companies. 'If testing becomes easier to do, there may be pressure to cut out the counselling that should go with it.'

Genetics and morality, page 23