Mutations linked to severe epilepsy in kids

U. MELBOURNE (AUS) / DUKE (US) — Advanced gene technology has revealed new mutations that cause epilepsy, a finding that could help steer treatment for the most severe forms of the disorder.

As part of a larger project analyzing 4,000 genomes from epilepsy patients around the world, researchers used exome sequencing to discover in one group of patients, two new genes and 25 epilepsy-causing mutations.

The research suggests there will be common pathways to target epilepsies with drugs and other therapies. Epilepsy affects an estimated 50 million people worldwide.


The study is a major conceptual advance in how epilepsies are analyzed, says Professor Sam Berkovic, director of the Epilepsy Research Centre at the University of Melbourne, and should help researchers to better identify their genetic causes and improve treatment options.

“These findings will help to fast track discoveries of the genetic causes of some of the most devastating childhood epilepsies, many of which had been previously unknown.”

Exomes essentially represent all of a person’s genes. Their DNA sequences provide the instructions for constructing all the proteins made by the body.

For the study, published in the journal Nature, researchers compared exome sequences of 264 children with the sequences of their parents who do not have epilepsy.  Differences in the sequences of these subject trios were analyzed using a number of statistical tools to identify potential disease causing mutations.

“This moderately sized study identified an unusually large number of disease-causing mutations and provides a wealth of new information for the epilepsy research community to explore,” says David Goldstein, director of the Human Genome Variation Center at Duke University Medical Center

“Solving the cause of these children’s epilepsy is a huge step forward in understanding why they are sick and the beginning of the development of targeted therapies,” says Ingrid Scheffer, a professor of pediatric neurology at the University of Melbourne.

Researchers estimate that up to 90 genes could carry epilepsy-causing mutations and that many of the mutations implicated in the risk of epilepsy have been previously associated with other neurodevelopmental diseases, including autism.

The study is part of a worldwide project, funded by the National Institutes of Health, called Epilepsy 4000 (Epi4K). The project’s mission is to use the latest genetic techniques to sequence and analyze DNA from 4,000 epilepsy patients and their relatives.

Source: University of Melbourne