Scientists identify gene linked to wasting disease

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The Independent Online
SCIENTISTS have identified a gene linked to certain inherited forms of motor neurone disease, a degenerative condition that kills more than a thousand people in Britain each year.

The discovery marks the latest breakthrough in research into the human genetic blueprint which is rapidly revealing the genes responsible for many of the 4,000 or more inherited disorders.

Although the discovery opens the way to a better understanding of the disease, and possibly a cure, it also raises ethical problems as it will almost certainly lead to a diagnostic test for an incurable disease that strikes carriers of the mutant gene in mid-life.

About 10 per cent of the 6,000 British sufferers of motor neurone disease have the inherited form of the condition. Both forms - the inherited and sporadic - produce similar symptoms, which begin with a shuffling gait and result in a progressive wasting of muscles and paralysis as nerves supplying them are gradually destroyed.

Professor Stephen Hawking, the wheelchair-bound theoretical physicist at Cambridge University, is the most famous sufferer of the non-inherited form of the disease. David Niven, the actor, Don Revie, the football manager, and Sir Leonard Cheshire VC, the war hero, all died from motor neurone disease.

Scientists hope the discovery will lead them to finding the cause of the disease. James McNamara, a medical researcher at Duke University Medical Centre in North Carolina said: 'We hope that understanding the familial form will provide a clue to the sporadic form. There is an outstanding possibility that the discovery will lead to prevention of the disease in terms of prenatal diagnosis and there is reason to hope it will lead to slowing the progression of the disease in sufferers.'

The discovery, published today in the journal Nature, was made by a team of 31 scientists from eight American research institutions, led by Robert Brown from the Massachusetts General Hospital. 'Their finding opens the door to a better understanding of the disease process and new ideas for therapeutic intervention,' Nature says.

By studying genetic material from 13 different families with a history of the disease, the scientists pinpoint mutations in a gene on chromosome 21 - one of the 23 pairs of human chromosomes.

The healthy gene normally produces a enzyme called superoxide dismutase which 'mops up' highly active toxins that damage nerve cells. The scientists believe that mutations interfere with normal production of the enzyme, leading to a build-up of toxins and gradual destruction of the muscle nerves. The toxin, said Dr McNamara, behaves like a 'bull in a china shop'.

Jaqueline de Belleroche, a motor neurone researcher at Charing Cross Hospital in London, said: 'What scientists need to do now is to prove that mutations in the gene are the cause of the disease. They need to show that mutations alter the function of the enzyme.'

She said that not all familial forms of motor neurone disease were linked with the gene on chromosome 21. 'There are probably two or more genes involved.'

Carriers of the defective gene live a normal healthy life until the first symptoms begin to appear, usually in middle age. Death typically follows within five years, making motor neurone disease a bigger killer than multiple sclerosis and muscular dystrophy.

A prenatal diagnostic test for the defective gene raises important ethical problems as couples face the prospect of aborting a foetus that could have 40 or more years of normal, active life, said Peter Cardy, director of the Motor Neurone Disease Association.

Women who choose to take the test will, if found positive, also learn whether they or their partners carry the defective gene and so will know that they will develop the condition in mid-life.


Examples of inherited disorders where genes have been found:

Cystic fibrosis

Duchenne's muscular dystrophy

G6PD deficiency causing acute anaemia

ADA immune deficiency

Tay-Sachs disease

'Lorenzo's oil' disease:


Thalassaemia: common anaemia

Menkes' disease


Lesch-Nyhan syndrome

Retinitis pigmentosa - inherited blindness

Aniridia blindness: babies born with no iris

Waardenburg's syndrome: inherited deafness

X-linked mental retardation in boys

Alzheimer's disease

Inherited disorders where genes may soon be found:

Inherited breast cancer

Certain forms of asthma

Inherited forms of diabetes

Some forms of heart disease

High blood pressure