A Dublin-based genetics specialist has helped trace a gene responsible for a condition affecting one in 6,000 new babies, often leading to severe complications such as epilepsy and autism.
The work on the tuberous sclerosis gene was carried out by international research teams which included Dr Andrew Green, professor of medical genetics at University College Dublin, and the director of the National Centre for Medical Genetics at Our Lady's Hospital for Sick Children, Crumlin.
Tuberous sclerosis is a common genetic condition which causes tumours in many parts of the body. Although the tumours are usually benign, they can lead to many medical problems, including epilepsy, learning difficulties, behaviour problems, autism and kidney and skin problems. Learning disability (mental handicap) is found in half the patients.
Although many with the condition have less severe problems and lead normal lives, they have the worry that a very mildly affected parent may have a severely affected child, or a mildly affected child may have a severely affected brother or sister.
The breakthrough, published today in Science journal, will lead to improved diagnosis and more effective genetic counselling, raising the possibility of better treatment, if not a cure. It is the culmination of 10 years' work involving six research teams in Europe and the US. Prof Green was affiliated to a research team from the University of Cambridge.
The disease is caused by a fault in either of two genes. One, TSC2, was discovered in 1993 and probably accounts for half the families with the disease. The other, TSC1, has been known since 1987 but defied identification until this year. The teams have succeeded in finding the gene by pooling their different areas of expertise over the past two years when "they decided to stop competing and to tackle the problem together", according to Prof Green.
The challenge was to track down the responsible gene from nearly two million "base pairs of DNA" (the letters of the genetic code). The normal DNA sequence of these two million bases was unknown and it was possible that the changes responsible for the disease might be tiny, just a single incorrect letter. The normal version was painstakingly charted and then it was possible, within weeks, to find small mistakes in the genetic code of affected people.
"The finding brings new hope to families where someone has tuberous sclerosis. Now both genes have been found we can think seriously about DNA tests for the condition. This will make diagnosis more certain and permit reliable genetic counselling for those worried about passing the condition on to their children," said Prof Green.
Many affected Irish families, members of the Tuberous Sclerosis Association of Ireland, have contributed to the research. Its chairwoman, Ms Margaret Manning, said: "The finding of the TSC1 gene is fantastic news. We are very excited about this research. It will make a real difference to families with tuberous sclerosis."
