Vanderbilt University researchers have identified a new gene that can influence a person's risk for developing epilepsy. The findings, reported in the March 29 Proceedings of the National Academy of Sciences, could improve molecular diagnostic tools and point to novel therapeutic targets for epilepsy.
The gene, KCNV2, codes for a unique type of potassium channel, a protein that participates in the electrical activity of nerve cells. Disturbed electrical activity in the brain and resulting seizures are hallmarks of epilepsy, a group of disorders that affects about 1 percent of the world's population.
A number of genetic mutations that cause inherited epilepsies have been identified. But the clinical severity of inherited epilepsies varies widely from mild childhood seizures that resolve with age to severe lifelong seizures even in individuals who have the same single-gene mutation, said Jennifer Kearney, Ph.D., assistant professor of Medicine in the Division of Genetic Medicine.
The range of clinical severity "tells us that there are other factors that contribute," she said. "We think that susceptibility and resistance genes that are inherited in addition to the primary mutation are probably a major factor."
Identifying susceptibility and resistance genes may suggest new targets for drugs that fine-tune neuronal excitability, rather than dampening it completely as many current antiepileptic drugs do, Kearney said.
The investigators began to look for these types of "modifier" genes after they made a curious observation in a mouse model of epilepsy that epilepsy severity depended on the genetic background strain of the mice.
They were studying mice with an epilepsy-causing gene mutation in a sodium channel, a protein that is important for neuronal excitability. The mice had spontaneous, progressive seizures and a reduced lifespan. But when the researchers "moved" the gene mutation into mice with a dif
|Contact: Leigh MacMillan|
Vanderbilt University Medical Center