Epilepsy genes may cancel each other

November 4, 2007

Inheriting two genetic mutations that can individually cause epilepsy might actually be “seizure-protective,” said Baylor College of Medicine researchers in a report that appears online today in the journal Nature Neuroscience.

“In the genetics of the brain, two wrongs can make a right,” said Dr. Jeffrey L. Noebels, professor of neurology, neuroscience and molecular and human genetics at BCM. “We believe these findings have great significance to clinicians as we move toward relying upon genes to predict neurological disease.”

In addition, the finding might point the way to new ways of treating epilepsy using gene-directed therapy.

“If you have a potassium channel defect, then a drug blocking certain calcium channels might also benefit you,” said Noebels.

Noebels and his colleagues, who included first author Dr. Ed Glasscock, a post-doctoral researcher at BCM, tested this hypothesis by breeding mice with two defective genes that govern ion channels, tiny pores in cells that allow molecules such as potassium and calcium to flow in and out.

The genes were known to cause epilepsy when inherited singly within families. They have also been found in a large-scale screen of people with non-familial seizure disorders being performed in collaboration with the Baylor Human Genome Sequencing Center.

One is a mutation in the Kcna1 gene involved in the channel that allows potassium to flow in and out of the cell. It causes severe seizures affecting the brain’s temporal lobe, an area of the brain involved in processing sight, sound, speech and forming memories. It can also cause sudden death in young mice.

The other mutation is in a calcium channel gene (Cacna1a) that causes a specific type of seizure associated with absence epilepsy. When people suffer these seizures, they may appear to be staring into space and do not exhibit the jerking or movements generally associated with epilepsy.

When both types of mutation occurred in the same young mouse, that animal had dramatically reduced seizures and did not suffer the sudden death associated with the potassium channel problem.

Noebels, who is also director of the Developmental Neurogenetics Laboratory funded by the National Institutes of Health and Blue Bird Circle Foundation, said, “Rather than screening for ‘bad’ genes one at a time, it may be essential to create a complete profile of many or even all genes in order to accurately assess the true genetic risk of any single defect in many common disorders such as epilepsy. Fortunately, this amount of background information will soon become routinely obtainable in individual patients thanks to rapid technological progress in the field of neurogenomics.”

Many different genes can lead to seizure disorders. In some cases, they encode ion channels that adjust the way neurons fire. Previous work indicated that combinations of such genes could make epilepsy worse. However, certain combinations may actually prevent the abnormal patterns of epilepsy, acting as “circuit breakers,” said Noebels.

Source: Baylor College of Medicine

Explore further: Potassium channel gene modifies risk for epilepsy

Related Stories

Potassium channel gene modifies risk for epilepsy

April 4, 2011

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 ...

Epilepsy halted in mice

August 3, 2009

Scientists at Leeds have prevented epilepsy caused by a gene defect from being passed on to mice offspring - an achievement which may herald new therapies for people suffering from the condition.

Epileptic seizures may be linked to an ancient gene family

August 1, 2010

New research points to a genetic route to understanding and treating epilepsy. Timothy Jegla, an assistant professor of biology at Penn State University, has identified an ancient gene family that plays a role in regulating ...

Gene identified for sudden unexpected death in epilepsy

April 13, 2010

A mutation in a brain protein gene may trigger irregular heart beat and sudden death in people with epilepsy, according to new research in the April 14 issue of The Journal of Neuroscience. People with epilepsy who are otherwise ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.