NIH Study on Childhood Epilepsies

More than 2 million people in the U.S. suffer from epilepsies and research studies show that infants and children have a greater chance of having the disorder than adults. Some studies have been able to find genes associated with rare inherited forms of epilepsy but finding genes associated with the majority of epilepsies has been difficult.

A genetic study of childhood epilepsies has linked two new genes to severe forms of the disease and provided a novel strategy for identifying therapy targets. The study used a cutting-edge genetic technique called exome sequencing to search for new mutations that are not inherited. The results suggest this may be a highly effective way to find and confirm many disease-causing gene mutations.

The study is part of a worldwide, $25 million project largely funded by NIH with additional funding provided by “Finding a Cure for Epilepsy and Seizures”, and the Richard Thalheimer Philanthropic Fund. The projects “Epilepsy 4000 (EPi4k) and Epilepsy Pheome/Genome Project (EPGP) were established to find genetic mutations that are not inherited”, said Randall Stewart, PhD, a Program Director at NINDS.

The aim is to use the latest genetic techniques to sequence and analyze DNA from 4000 epilepsy patients and their relatives. To do this, researchers have organized a team of international research institutions called “Epilepsy Centers Without Walls”.

The intention is to share and analyze DNA sequences and patient information among the dozens of institutions participating in the project. In the study published in “Nature” on EPi4K and EPGP, investigators found as many as 25 epilepsy-causing mutations in new and previously identified genes.

EPi4K and EPGP with its massive data set laid the groundwork for this study and the key to success has been the high level of collaboration among more than 115 investigations, study coordinators, and administrative personnel involved in both EPGP and EPi4K,” said Daniel Lowenstein MD, Vice Chair of the Department of Neurology at UCSF.

“One of the most encouraging aspects of this study is that we’re beginning to see how best to interpret and make effective use of exome sequence data,” said David Goldstein, PhD, Director of the Center for Human Genome Variation at Duke University Medical Center.

“We anticipate that further studies will identify many new disease-causing genes and we intend to develop a watch list of the genes that summarizes their clinical characteristics in a way that will be helpful for doctors, patients, and researchers.”