NIH-funded Study Discovers New Genes for Childhood Epilepsies

Ruth Ottman, PhD, professor of epidemiology was part of a 61-member international research team working to improve understanding of childhood epilepsy and other complex neurological disorders. Dr. Ottman was a principal investigator of two of the NIH grants that supported this work.

Researchers from the Epilepsy 4000 (Epi4K) group, of which Dr. Ottman is a member, used genomic analysis to search for mutations that are likely to be involved with severe childhood epilepsies. Dr. Ottman, who is also deputy director for research of Columbia’s Gertrude H. Sergievsky Center and professor in the Department of Neurology, is also a member of the Epilepsy Phenome/Genome Project (EPGP) team that collected clinical information on the families analyzed in this research.

The paper, whose findings are published in Nature, reports the discovery of as many as 25 epilepsy-causing mutations in new and previously identified genes. The National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH), supported the work as part of a $25 million program, and described the research in their recent news release:

A genetic study of childhood epilepsies has linked two new genes to severe forms of disease and provides a novel strategy for identifying therapy targets. This 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 the National Institutes of Health, called Epilepsy 4000 (Epi4K). Epi4K’s mission is to use the latest genetic techniques to sequence and analyze DNA from 4000 epilepsy patients and their relatives. To do this, the researchers and NIH staff involved organized a team of international research institutions devoted to the mission, called the Epilepsy Centers without Walls. This approach facilitates the sharing and analysis of DNA sequences and patient information among the dozens of institutions participating in the project.

“These promising results highlight the strength of supporting large international research teams devoted to studying the genetics behind highly complex neurological disorders,” said Story Landis, Ph.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS).

“Until recently, the extreme genetic and etiologic heterogeneity of the epilepsies has presented serious problems for gene discovery -- but thanks to an unprecedented international collaboration and the use of state-of-the art genomic analysis methods, we are finally making important progress” noted Dr. Ottman. “These new gene discoveries promise to lead to new understanding of mechanisms, and to development of new treatments for severe, childhood onset epilepsies.”

Read NINDS’s full news release about the findings.