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Potassium channel gene modifies risk for epilepsy
Date:4/4/2011

ferent genetic background (using breeding strategies), the epilepsy became less severe: the mice developed seizures later and had improved survival.

Using genetic strategies, the investigators zeroed in on two chromosome regions that influenced the difference in epilepsy severity in the two mouse strains. In one of these regions, the mouse Kcnv2 gene (the mouse equivalent of the human KCNV2 gene) appeared to be the strongest candidate gene, based on its potential for altering electrical activity in neurons.

The current report demonstrates that increased expression of the mouse Kcnv2 gene not changes in its coding sequence is associated with more severe epilepsy in the susceptible mouse strain. Increasing Kcnv2 expression in the resistant mouse strain caused these mice to develop more severe symptoms, supporting the gene's contribution as an epilepsy modifier.

The investigators then screened 209 pediatric epilepsy patients for variations in KCNV2 and found two different variations in two unrelated patients.

Colleagues in the laboratory of Alfred George Jr., M.D., director of the Division of Genetic Medicine, conducted electrophysiology studies in cells to examine how the two variations affected the function of the potassium channel. They found that both variations suppressed a type of potassium current that normally dampens excitability in neurons.

"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 team plans to screen additional patients with epilepsy to assess the incidence of variations in KCNV2. They are also collaborating with Dave Weaver, Ph.D., director of the Vanderbilt High-Throughput Screening Facility, to find compounds that target the potassium channel and may be useful therapeutics for epilepsy.

Kearney said that understanding how genes such as KCNV2 modify the clinical severity of
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Contact: Leigh MacMillan
leigh.macmillan@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert  

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