A team of researchers has pinpointed two genes that, when mutated, can each cause epilepsy in infants. Although these mutations are relatively rare, their discovery, reported in the January issue of Nature Genetics, could help point the way to other genes behind inherited epilepsies, which are thought to account for about 40% of all forms of the disease. Other types of epilepsy are caused by injuries to the brain and infectious diseases.
Mark Leppert and his colleagues at the University of Utah in Salt Lake City, and other institutions, discovered the culprit mutations when they were looking for the cause of two epilepsies called benign familial neonatal convulsions. In these conditions, infants only a few days old suffer frequent seizures, which usually cease after a few weeks, leaving them with 8 times of risk of having seizures as adults.
Leppert and his colleagues found that several afflicted people in families with a high incidence of this condition had mutations in small sections of chromosome 20. By comparing this region with the DNA from epileptics from six other families, the researchers gradually homed in on a gene called KCNQ2. This gene codes for part of a pore in nerve cells called a potassium channel that is vital for transmitting nerve impulses to adjoining cells.
The researchers hypothesize that when the gene is mutated, the potassium channel cannot flush potassium out of the cell and reset the nerve cell for a new transmission. This defect, they speculate, somehow allows uncontrolled transmissions of nerve signals and leads to spasmodic seizures. The team also ferreted out another potassium channel gene called KCNQ3 that was mutated in two families, and apparently causes a nearly identical form of the disease.
Other epilepsy researchers, such as Wayne Frankel, a molecular geneticist at The Jackson Laboratory in Bar Harbor, Maine, say these findings should be helpful because potassium channel defects probably play a role in other inherited forms of epilepsy. But there could easily be hundreds of epilepsy genes, he says, many of which may not be affecting potassium channels.