Featured Research

from universities, journals, and other organizations

Largest study of epilepsy patients ever conducted reveals new and surprising genetic risk factors

August 12, 2013
NYU Langone Medical Center / New York University School of Medicine
Neurologists and epilepsy researchers have discovered 329 random genetic mutations associated with two of the most severe forms of epilepsy, according to a new article.

Neurologists and epilepsy researchers from NYU Langone Medical Center were among scientists who have 329 random genetic mutations associated with two of the most severe forms of epilepsy, according to a paper published today in Nature. Though well-known that many forms of epilepsy are strongly influenced by genetics, there has been relatively little progress in identifying the genetic differences that contribute to most forms of epilepsy. This study sheds light on why some with an elevated risk for epilepsy never get the disease and why certain medications work better for some patients than others.

Related Articles

"For generations we have been treating most forms of generalized epilepsies with no idea what causes the disease. Now, for the first time, we have identified clear genetic risk factors in patients with severe epilepsy," says study co-author Ruben Kuzniecky, MD, professor of neurology at NYU Langone Medical Center, where he serves as co-director of the NYU Comprehensive Epilepsy Center and director of epilepsy research.

The findings are the first to emerge from the largest investigation into the genetics of epilepsy ever conducted. The study, known as the "Epilepsy Phenome/Genome Project" (EPGP) and representing a consortium of 27 medical centers from around the world, is led by Dr. Kuzniecky and Daniel Lowenstein, MD, professor and vice chair of the Department of Neurology at the University of California, San Francisco (UCSF), and director of the UCSF Epilepsy Center. Since 2007, when the project began, its team of several hundred physicians and staff has collected blood samples and clinical information from more than 4,000 patients with epilepsy and their family members. NYU Langone contributed data for 430 patients, representing the largest enroller in the study. The researchers expect the project's unprecedented dataset to yield results for several years to come.

"This project is one of the most ambitious undertakings in our field," Dr. Kuzniecky says. "It won't be long before it leads to genetic tools that will help us diagnose patients more accurately and tailor treatments specific to their form of epilepsy."

The goal of the project is to find molecular targets that will transform the way epilepsy, a neurological condition characterized by abnormal electrical activity in the brain that causes chronic seizures, is diagnosed and treated. One of the most common neurological disorders, epilepsy affects 1-2 in 100 people worldwide. For most forms of epilepsy, the cause is unknown, but scientists believe genetics play an important role. The risk of epilepsy among people who have parents or siblings with the disorder is about 4 to 8 percent, whereas the risk in the general population is 1 to 2 percent. Yet scientists have discovered only a handful of genes linked to rare forms of epilepsy in only a small number of people.

For more common types of epilepsy, including the two investigated in this study -- infantile spasms and Lennox-Gastaut syndrome -- the condition is thought to arise from a combination of inherited mutations and random mutations that occur after birth, called de novo mutations. Identifying these de novo mutations is critical to understanding why some people with a family risk of the disease never develop it, while others do, and why certain medications are more effective in some patients than others.

In the study, partly funded through a $15 million grant from the National Institute of Neurological Disorders and Stroke, researchers sequenced DNA extracted from the blood samples of 149 children with infantile spasms, or West Syndrome, a type of seizure associated with severe developmental problems that often affects infants between 4 to 8 months old, and 115 patients with Lennox-Gastaut Syndrome, characterized by seizures in childhood that do not respond to therapy and also cause severe developmental problems. The researchers also analyzed the DNA of parents who do not have the disease, allowing them to isolate genetic mutations in children with epilepsy that arise at or during birth.

The study analysis revealed de novo (random) mutations on nine specific genes with four mutations being completely new ones never before associated with epilepsy. "We found that each mutation carries substantial risk for these forms of epilepsy," says Dr. Kuzniecky. "It's clear that rare individual mutations in different genes converge on specific biological pathways, suggesting a clear direction for personalized therapy and drug development."

Why certain genes are more vulnerable to mutations than others, and why people develop different forms of epilepsy, remains unknown. "Two people could have the same mutation, but express it differently clinically," explains Dr. Kuzniecky. "But we know that the disease follows certain patterns." The mutations were also found to overlap with autism spectrum disorder and severe developmental disorders, suggesting that the disorders may share common molecular miscues.

Story Source:

The above story is based on materials provided by NYU Langone Medical Center / New York University School of Medicine. Note: Materials may be edited for content and length.

Journal Reference:

  1. Andrew S. Allen, Samuel F. Berkovic, Patrick Cossette, Norman Delanty, Dennis Dlugos, Evan E. Eichler, Michael P. Epstein, Tracy Glauser, David B. Goldstein, Yujun Han, Erin L. Heinzen, Yuki Hitomi, Katherine B. Howell, Michael R. Johnson, Ruben Kuzniecky, Daniel H. Lowenstein, Yi-Fan Lu, Maura R. Z. Madou, Anthony G. Marson, Heather C. Mefford, Sahar Esmaeeli Nieh, Terence J. O'Brien, Ruth Ottman, Slavι Petrovski, Annapurna Poduri, Elizabeth K. Ruzzo, Ingrid E. Scheffer, Elliott H. Sherr, Christopher J. Yuskaitis, Bassel Abou-Khalil, Brian K. Alldredge, Jocelyn F. Bautista, Samuel F. Berkovic, Alex Boro, Gregory D. Cascino, Damian Consalvo, Patricia Crumrine, Orrin Devinsky, Dennis Dlugos, Michael P. Epstein, Miguel Fiol, Nathan B. Fountain, Jacqueline French, Daniel Friedman, Eric B. Geller, Tracy Glauser, Simon Glynn, Sheryl R. Haut, Jean Hayward, Sandra L. Helmers, Sucheta Joshi, Andres Kanner, Heidi E. Kirsch, Robert C. Knowlton, Eric H. Kossoff, Rachel Kuperman, Ruben Kuzniecky, Daniel H. Lowenstein, Shannon M. McGuire, Paul V. Motika, Edward J. Novotny, Ruth Ottman, Juliann M. Paolicchi, Jack M. Parent, Kristen Park, Annapurna Poduri, Ingrid E. Scheffer, Renιe A. Shellhaas, Elliott H. Sherr, Jerry J. Shih, Rani Singh, Joseph Sirven, Michael C. Smith, Joseph Sullivan, Liu Lin Thio, Anu Venkat, Eileen P. G. Vining, Gretchen K. Von Allmen, Judith L. Weisenberg, Peter Widdess-Walsh, Melodie R. Winawer. De novo mutations in epileptic encephalopathies. Nature, 2013; DOI: 10.1038/nature12439

Cite This Page:

NYU Langone Medical Center / New York University School of Medicine. "Largest study of epilepsy patients ever conducted reveals new and surprising genetic risk factors." ScienceDaily. ScienceDaily, 12 August 2013. <www.sciencedaily.com/releases/2013/08/130812103004.htm>.
NYU Langone Medical Center / New York University School of Medicine. (2013, August 12). Largest study of epilepsy patients ever conducted reveals new and surprising genetic risk factors. ScienceDaily. Retrieved January 26, 2015 from www.sciencedaily.com/releases/2013/08/130812103004.htm
NYU Langone Medical Center / New York University School of Medicine. "Largest study of epilepsy patients ever conducted reveals new and surprising genetic risk factors." ScienceDaily. www.sciencedaily.com/releases/2013/08/130812103004.htm (accessed January 26, 2015).

Share This

More From ScienceDaily

More Health & Medicine News

Monday, January 26, 2015

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Mistakes Should Serve a Lesson Says WHO

Ebola Mistakes Should Serve a Lesson Says WHO

AFP (Jan. 25, 2015) — The World Health Organization&apos;s chief on Sunday admitted the UN agency had been caught napping on Ebola, saying it should serve a lesson to avoid similar mistakes in future. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Disneyland Measles Outbreak Spreads To 5 States

Disneyland Measles Outbreak Spreads To 5 States

Newsy (Jan. 24, 2015) — Much of the Disneyland measles outbreak is being blamed on the anti-vaccination movement. The CDC encourages just about everyone get immunized. Video provided by Newsy
Powered by NewsLook.com
Growing Measles Outbreak Worries Calif. Parents

Growing Measles Outbreak Worries Calif. Parents

AP (Jan. 23, 2015) — Public health officials are rushing to contain a measles outbreak that has sickened 70 people across 6 states and Mexico. The AP&apos;s Raquel Maria Dillon has more. (Jan. 23) Video provided by AP
Powered by NewsLook.com
Smart Wristband to Shock Away Bad Habits

Smart Wristband to Shock Away Bad Habits

Reuters - Innovations Video Online (Jan. 23, 2015) — A Boston start-up is developing a wristband they say will help users break bad habits by jolting them with an electric shock. Ben Gruber reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.


Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News


Free Subscriptions

Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile

Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?

Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins