Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Genes for Childhood Epilepsies Discovered

Published: Monday, August 12, 2013
Last Updated: Monday, August 12, 2013
Bookmark and Share
New strategy may find more genes and provide a better understanding of these and other complex neurological disorders.

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.

“It appears that the time for using this approach to understand complex neurological disorders has arrived,” said David Goldstein, Ph.D., director of the Center for Human Genome Variation at Duke University Medical Center, Durham, N.C., and a leader of the study. “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.”

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. The study, published in Nature by the Epi4K and Epilepsy Phenome/Genome Project (EPGP) Investigators, found as many as 25 epilepsy-causing mutations in new and previously identified genes.

“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). The project is also led by Daniel Lowenstein, M.D., a vice chair of the Department of Neurology at the University of California, San Francisco (UCSF) and Sam Berkovic, M.D., director of the Epilepsy Research Center at the University of Melbourne, Australia on behalf of an international team of investigators.

Epilepsy is a group of neurological disorders caused by abnormal firing of nerve cells in the brain which often produces debilitating seizures and a range of other symptoms. More than 2 million people in the United States suffer from epilepsies, and infants and children have a greater chance of having the disorders than adults. Although some studies have found genes associated with rare inherited forms of epilepsy, finding genes associated with the majority of epilepsies has been difficult.

“Unlike some diseases many of the genetic mutations associated with severe childhood epilepsies appear to be new mutations that are not inherited,” said Randall Stewart, Ph.D., a program director at NINDS. “This Epi4K-EPGP project was established to find such mutations.”

In this study, the researchers used exome sequencing to find mutations that might cause two devastating forms of childhood epilepsy, called infantile spasms and Lennox-Gastaut Syndrome. DNA and clinical data were originally collected through the NIH-funded Epilepsy Phenome/Genome Project which was led by Dr. Lowenstein and Elliot Sherr, M.D., Ph.D., director of the Comprehensive Center for Brain Development at UCSF and Dr. Ruben Kuzneicky, M.D., professor at the New York University Comprehensive Epilepsy Center.

“The Epilepsy Phenome/Genome Project, with its massive data set, laid the groundwork for this study, and the key to this success has been the extraordinary level of collaboration among more than 115 investigators, study coordinators and administrative personnel involved in both EPGP and Epi4K,” said Dr. Lowenstein.

Exomes essentially represent all of a person’s genes. Their DNA sequences provide the instructions for constructing all the proteins made by the body. The 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. Compared with some genetic studies, this research sequenced DNA from relatively few patients. Nonetheless, the researchers were able to find disease-causing mutations in six genes: four had been described before using other genetic techniques and two genes are implicated for the first time.

Using novel genetic analysis techniques, the researchers also demonstrated that epilepsy-causing mutations are concentrated in genes that are highly sensitive, or intolerant, to changes in their DNA sequence in human populations. These genes are so sensitive that even the slightest change can cause the gene not to work, leading to death or severe forms of diseases.

“This study used a very sophisticated bioinformatics approach to analyze DNA sequences and find disease-causing mutations,” said Katrina Gwinn, M.D., a program director at NINDS.

To find more genes that are likely to have epilepsy-causing mutations, the researchers searched thousands of exome sequences from healthy volunteers who participated in the National Heart Lung and Blood Institute Exome Sequencing Project. They looked for gene sequences that had only slight differences among subjects because previous studies showed that these sequences are highly sensitive to mutations. The researchers estimated 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.

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

For instance, the researchers analyzed how the genes that could carry epilepsy-causing mutations work and interact. Their analysis showed that the genes can be grouped into a few networks. Each network appears to play an important role in the growth and development of a child’s nervous system.

“It appears that a few pathways may be responsible for many severe pediatric epilepsies,” said Dr. Goldstein, “If true, then understanding epilepsies will be more manageable and we can find common pathways to target with drugs and other therapies.”

In addition to grants from NINDS (NS053998, NS077364, NS077274, NS077303, NS077276), this study was funded by Finding a Cure for Epilepsy and Seizures and the Richard Thalheimer Philanthropic Fund.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Visual Impairment, Blindness Cases in U.S. Expected to Double by 2050
Researchers at NIH have suggested that there is a need for increased screening and interventions to identify and address treatable causes of vision loss.
Friday, May 20, 2016
Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
NIH Funds New Studies on Ethical, Legal and Social Impact of Genomic Information
Four new grants from the National Institutes of Health will support research on the ethical, legal and social questions raised by advances in genomics research and the increasing availability of genomic information.
Wednesday, May 18, 2016
Large-scale HIV Vaccine Trial to Launch in South Africa
NIH-funded study will test safety, efficacy of vaccine regimen.
Wednesday, May 18, 2016
New HIV Vaccine Target Discovered
NIH-Led team have discovered a new vaccine target site on HIV.
Tuesday, May 17, 2016
Researchers Identify Genetic Links to Educational Attainment
Researchers at NIH have suggested that the large genetics analyses may be able to help discover biological pathways as well.
Thursday, May 12, 2016
Investigational Malaria Vaccine Protects Healthy U.S. Adults
Researchers at NIH have found that the malaria vaccine protected a small number of healthy, malaria-naïve adults in the U.S. from infection for more than one year after immunization.
Tuesday, May 10, 2016
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Thursday, May 05, 2016
Finding Factors That Protect Against Flu
A clinical trial examining the body’s response to seasonal flu suggests new approaches for evaluating the effectiveness of seasonal flu vaccines.
Wednesday, April 27, 2016
Factors Influencing Influenza Vaccine Effectiveness Uncovered
The long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited, new research suggests.
Thursday, April 21, 2016
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Serotonin Transporter Structure Revealed
Researchers determined the 3-D structure of the serotonin transporter and visualized how two common antidepressants interact with the protein.
Wednesday, April 20, 2016
Improving Flu Vaccine Effectiveness
NIH study finds factors that may influence influenza vaccine effectiveness.
Wednesday, April 20, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
Migration Creates Cancer Cell Vulnerabilities
Scientists found that migration can damage cancer cells’ nuclei and DNA, requiring repairs for their survival. The results may open new avenues for targeting metastatic cancer.
Wednesday, April 13, 2016
Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
World’s Largest Coral Gene Database
‘Genetic toolkit’ will help shed light on which species survive climate change.
A Boost for Regenerative Medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Breast Cancer Drug Hope
A drug for breast cancer that is more effective than existing medicines may be a step closer thanks to new research.
Untangling Disease-Related Protein Misfolding
Work advances understanding of genetic forms of thrombosis, emphysema, cirrhosis of the liver, neurodegenerative diseases and inflammation, among others.
Early Genetic Changes in Premalignant Colorectal Tissue Identified
Findings point to drivers of early cancer development, targets for cancer prevention therapies.
Scientists Find Evidence That Cancer Can Arise Changes
Researchers at Rockefeller University have found a mutation that affects the proteins that package DNA without changing the DNA itself can cause a rare form of cancer.
Developing a More Precise Seasonal Flu Vaccine
During the 2014-15 flu season, the poor match between the virus used to make the world’s vaccine stocks and the circulating seasonal virus yielded a vaccine that was less than 20 percent effective.
A Peachy Defense System for Seeds
ETH chemists are developing a new coating method to protect seeds from being eaten by insects. In doing so, they have drawn inspiration from the humble peach and a few of its peers.
Fighting Cancer with Borrowed Immunity
A new step in cancer immunotherapy: researchers from the Netherlands Cancer Institute and University of Oslo/Oslo University Hospital show that even if one's own immune cells cannot recognize and fight their tumors, someone else's immune cells might.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!