Potassium channel gene modifies epilepsy risk
Epilepsy – a group of disorders characterized by disturbed brain electrical activity and seizures – affects about 1 percent of the world’s population.
Inherited epilepsies can be caused by a number of different genetic mutations. But the clinical severity of inherited epilepsies, even in individuals who have the same single-gene mutation, varies widely – from mild childhood seizures that resolve with age to severe lifelong seizures.
The range of clinical severity “tells us that there are other factors that contribute,” said Jennifer Kearney, Ph.D., assistant professor of Medicine at Vanderbilt University School of Medicine. “We think that susceptibility and resistance genes that are inherited in addition to the primary mutation are probably a major factor.”
Now, Kearney and colleagues including Alfred George Jr., M.D., director of the Division of Genetic Medicine, have identified a susceptibility gene that can influence a person’s risk for developing epilepsy.
The gene, KCNV2, codes for a unique type of potassium channel, a protein that participates in the electrical activity of nerve cells. The researchers found that variations in the gene – discovered in pediatric patients with epilepsy – affected the function of the potassium channel.
“The mutations make a neuron more excitable, so you could have longer periods of excitation and also repetitive excitation (that leads to seizures),” Kearney said.
The findings, reported in the Proceedings of the National Academy of Sciences, could improve molecular diagnostic tools and point to novel
targets for antiepileptic drugs that fine-tune neuronal excitability.