Sodium channel gene mutation identified in case of familial epilepsy

Researchers at Emory University have identified a specific mutation in a sodium channel gene (SCN1A) that is associated with epilepsy syndrome in a family. The findings were presented at the American Academy of Neurology in San Francisco on Tuesday, April 27th . The finding adds to a growing body of information about links between genetic mutations and epilepsy; more than two dozen genes implicated in the disease have been discovered to date, according to the Epilepsy Foundation.

“The premise of this study was to enroll families with neurological diseases in which the genetic cause is unknown,” says Salina Waddy, MD, associate and post-doctoral fellow in the Department of Neurology, Emory University School of Medicine. “Identifying this novel mutation in a sodium channel gene (SCN1A) on Chromosome 2, which is associated with epilepsy will, in the end, help us learn how to better treat patients and their families who have a type of familial epilepsy called generalized epilepsy with febrile seizures plus (GEFS+).”

Six Caucasian family members who all had GEFS+ were enrolled in the Emory study. GEFS+ is described as a condition where unusual bursts of energy discharge across the entire brain simultaneously, resulting in a seizure that is sometimes associated with high fevers. In most people who have febrile seizures, the seizures go away before the age of 6. In these patients, their febrile seizures occasionally persist beyond age 6, hence the “plus” in the GEFS+ name.

A physical exam, MRI and EEG analyses (electroencephalogram or brain electrical activity recording) were performed on the family member who attends the Emory Epilepsy Clinic in order to confirm the diagnosis. Other family members were interviewed by telephone and medical histories were documented and corroborated by other family members. Once completed, blood samples were taken and DNA was isolated. The researchers then screened the genes in which other GEFS+ mutations have been previously identified and discovered the mutation known as R859C.

“The whole genetic basis of epilepsy is exploding,” says Sandra Helmers, MD, associate professor of neurology, Emory University School of Medicine. “The genes for this one particular form of inherited epilepsy (GEFS+) were initially described in the late 90s. This new finding allows us to think about epilepsy in a different light and realize that some epilepsies do run in families. This finding will also allow us to look at better diagnoses, treatments and better genetic counseling for this population.”

The study was funded by grants from the Citizens United for Research in Epilepsy (CURE) and the March of Dimes and is a collaboration between members of Emory’s Departments of Neurology and Human Genetics.

“Collaborations such as these are the key to translational research, which will benefit patient care in the long term,” says Andrew Escayg, PhD, assistant professor of human genetics in the Emory University School of Medicine. “Multidisciplinary research is becoming more and more important when studying complex neurological disorders, such as epilepsy.”

The team of researchers is also trying to identify novel or new genes in other neurological disorders, such as neuromuscular diseases, ataxia, sleep disorders and dystonia.

“By identifying genes and mutations in these specific neurological disorders, we should be able to give more precise care to our patients, as well as give them better answers about their disorders,” says Dr. Waddy. “And, with our recent finding in this form of familial epilepsy, I think we are on the right track.”

The GEFS+ mutation presentation will be highlighted in two other scientific sessions during the American Academy of Neurology Conference.

Media Contact: Janet Christenbury, 404-727-8599, jmchris@emory.edu.