11-09-2014 | RCSI researchers play key role in international collaboration uncovering the genetic mysteries of epilepsy

11 September 2014
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RCSI (Royal College of Surgeons in Ireland) researchers played a leading role in a study recently published in the Lancet Neurology that has made an important step in discovering that whether we develop epilepsy or not may be determined by the combination of genes we inherit. More than 34,000 people were involved in this genetic study, of which more than 8,000 had epilepsy. The study participants were of European, Asian and African ancestry.

This work was supported in part, by Epilepsy Ireland and the Health Research Board via a research grant to Dr Gianpiero Cavalleri and colleagues at the RCSI.

The study found that two genes stood out as having broad implications for epilepsy. One, a sodium channel subunit that regulates neuronal excitability (SCN1A), had previously been associated with certain familial and severe childhood epilepsies; this finding suggests it has an even broader role. 

A second gene for the protein 'protocadherin', which helps bind cells together, was also strongly associated with epilepsy. This discovery was unexpected and suggests that the factors that contribute to common epilepsies are more complex than originally thought, and may involve the basic structure of the brain. 

Prof. Norman Delanty, RCSI Dept of Molecular and Cellular Therapeutics and Beaumont Hospital said 'This is a important milestone in our efforts to understand the genetics of epilepsy. Most people with epilepsy do not have a strong family history of the condition, but we know genes still play an important role. This work provides insight to the particular genetic factors that contribute to epilepsy in this population".

Since the first identification of a single gene mutation that caused a particular type of epilepsy that ran in a family (Autosomal Dominant Nocturnal Frontal Lobe Epilepsy), the search for the inherited cause of epilepsy focused on families in which many members had the disease. It became clear that there were a number of such genes causing familial epilepsies but there were family members who carried one of these genes but who did not have the disease. 

Previous studies revealed that there was more to the development of epilepsy than the single gene mutation. Subsequent research showed that epilepsies of all kinds were more common in some families than in others. That observation led epilepsy researchers to conclude that the risk for epilepsy was related to multiple genetic factors. Determining those factors among the thousands of genes active in people would greatly improve our understanding of the biology of epilepsy.

Due to the the huge variability in each person's genetic makeup, finding the genes that increase the risk required evaluating thousands of people from different countries and different ethnic backgrounds. The International League Against Epilepsy with its global reach created the ILAE Consortium on Complex Epilepsies in order to bring researchers together to increase the efforts in developing better treatments for the disease.

Emilio Perucca, President of the International League Against Epilepsy commented, "We are very pleased that the League has been able to bring together this outstanding group of researchers in our efforts to provide better treatments for the disease. It is a great example of how an international organization can play a key role in bringing people together around a common goal. We were particularly fortunate to recruit a young geneticist, Christopher Whelan, to assist with the analysis for the study. Christopher worked under the leadership of Prof. Norman Delanty and Dr. Gianpiero Cavalleri of the Royal College of Surgeons in Ireland and Dr. Colin Doherty of St. James' Hospital Dublin. Their extraordinary skills in these types of studies were key to the success of this effort." 

Read the study here:

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