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Epilepsy genetic defect discovered

4 Mar 2003

Research scientists at the Universities of Bonn, Ulm and Aachen have identified a gene that, if not properly functioning, can trigger all forms of commonly occurring idiopathic epilepsy (where seizures have no apparent cause).

Dr Armin Heils, from the University of Bonn, said:

"We make an overall distinction between seven different types of so-called idiopathic epilepsies. The most dangerous are referred to as 'grand mal' (tonic-clonic) seizures, which are associated with loss of consciousness and severe muscle cramps. What all these forms have in common is that they tend to run in the family. The predisposition is inherited, and some rare types are actually caused by a single gene defect."

Every nerve cell communicates with numerous neighbouring cells via electrical impulses. A seizure occurs when these impulses proliferate. A single initial signal can then lead to an electrical response on millions of nerve cells. This is normally prevented by a tiny messenger substance known as "GABA" which makes the nerve cells less excitable.

The ability of GABA to constrain the process of signal proliferation depends, on the concentration of chloride in the nerve cells. If it is too high, the messenger substance acts more like an accelerator. The epilepsy gene contains a blueprint for a channel through which chloride ions from the nerve cells can escape. If an error has been written into the blueprint, the channel becomes useless and the chloride concentration rises in the cells, so that GABA can no longer developed the desired action. Seizures are the consequence.

For the study, published in the journal Nature Genetics, the researchers studied a total of 46 families in which at least two members had idiopathic epilepsy.

Dr Heils commented that in three families, the gene for the chloride channel had mutated; all the family members with epilepsy had inherited the defective gene, while those members without epilepsy hadn't. In one of these families the channel remained partially functional despite the mutation; these patients have suffered only rare seizures, which were milder than those found in the other two families. The study found that the patients had different forms of idiopathic epilepsy suggesting that this was an indication that other genes play a role in the disorder. In contrast, the researchers looked at a control group of 360 people without epilepsy and found no changes in the channel gene.