Epilepsy susceptibility gene pinpointed

Researchers at the Women's and Children's Hospital (WCH) in Adelaide have identified variations in an ion channel gene that increases susceptibility to the most common form of epilepsy.

Along with collaborators at Adelaide biotech company Bionomics, and researchers at the University of Melbourne and the US's Vanderbilt University, the Adelaide scientists led by Dr John Mulley and Dr Leanne Dibbins identified two variations in the GABRD gene, which encodes the delta subunit of the GABA-A receptor, associated with an increased susceptibility to generalised epilepsies. The study was published online in the journal Human Molecular Genetics on April 28, 2004.

Mulley, who heads the Molecular Genetics laboratory at WCH, said that the association of mutations in other GABA-A subunit genes with particular forms of epilepsy had suggested to the researchers that additional mutations linked to susceptibility to epilepsy might be found in other subunits. A population of 203 patients with various forms of generalised epilepsies were screened for mutations in the GABRD gene.

The researchers found that two out of three variations of the gene in the sampled population resulted in a decrease in the receptor current amplitude measured, suggesting that as the GABA-A receptor inhibits neuronal excitation, increased neuronal excitability might result. One of the mutations was found in members of a family with generalised epilepsy with febrile seizures plus (GEFS+), while the other was found in about five per cent of the general population as well as at a similar frequency in patients with various forms of generalised epilepsies.

A third variation identified by the researchers appears to have no functional effect on the receptor, and further investigation of the gene is continuing, Mulley said.

Mulley noted that the low frequency of the variations in the population suggested that the GABRD variations were just one component of a system involving many genes.

"Epilepsy affects 3 per cent of the world's population at some time in their life although it is most common in the young and the old. This gene adds to the risk of being affected with the common forms of epilepsy that affect 40 per cent of these people," he said.

"Many people in the general population have changes in the gene which, in themselves, are not sufficient to cause epilepsy. There are other factors involved such as similar changes in other, still to be discovered, genes together with environmental factors."

Mulley said the team had an unusual setup with laboratories at Bionomics' facility in Adelaide, where the academic scientists worked hand in hand with the company's scientists. Bionomics funds the research and has the rights to develop IP.

"It's a fairly unique arrangement," he said.