The identification of the gene - one of two thought to be responsible for the condition - opens the way to predictive tests for families at risk of having children suffering from the disease, which had previously seemed to strike without warning.
Tuberous sclerosis is a relatively common inherited disease - about 1 in 6,000 people is affected - which can cause mental handicap, epilepsy, disfiguring skin rashes and kidney disorders. The faulty gene causes abnormal development of tuber-like growths in the brain which become hard or sclerotic, hence the condition's name (it has no relationship to multiple sclerosis, nor to tuberculosis).
But the scientists who found the gene were intrigued to discover that it produces a protein, known as tuberin, which resembles a molecule, GAP3, known to be involved in regulating the growth and proliferation of cells - and thus playing a role in cancer. Patients with tuberous sclerosis frequently develop tumours, but these are almost always benign.
Dr Julian Sampson, from the Institute of Medical Genetics at Cardiff and one of the leaders of the research group that discovered the gene, said: 'It's likely that in some tumours abnormalities of this protein may exist.'
Dr Sampson believes that two practical applications will follow from the discovery. 'The condition is renowned for the variability of its severity and because the condition is so very variable, members of families are unsure as to whether they are carrying the gene or not. The hope is that a more direct, gene- based test could be developed.'
A single copy of the defective gene is sufficient to cause the disease, and anyone carrying the faulty gene has a one in two chance of passing it on to his or her children.
Because of the variation in its severity, someone with minimal or no manifestations of tuberous sclerosis could have the gene which could then severely affect their offspring.
The development of a test is complicated because researchers know that the gene, whose identification is published in the scientific journal Cell today and which lies on the 16th of the 24 human chromosomes, is responsible for only half of the cases of tuberous sclerosis. The other cases stem from a mutation in a gene lying on chromosome number 9 which has not yet been identified.
Paradoxically, the existence of a genetic defect on chromosome 9 linked to tuberous sclerosis was proved in 1987, whereas the existence of a defect on chromosome 16 came to light only last year. This gene was speedily isolated and identified because four groups of researchers 'were working together rather than competing', and because the techniques for identifying genes are getting faster, Dr Sampson said.
The second practical application is the development of some form of treatment, but Dr Sampson cautioned that the nature of the disease makes it unlikely that it could be a good candidate for gene therapy. 'Because it affects so many organs, especially the brain, it's difficult to see how you can deliver intact genes to all the organs,' he said. But by understanding the mechanisms of the disorder, Dr Sampson believes, it may be possible to devise other therapies for the condition.Reuse content