This largest whole-genome sequencing study on epilepsy was piloted by Jacques Michaud, Pediatrician at CHU Sainte-Justine and Professor of Pediatrics and Neuroscience at the Faculty of Medicine of Université de Montreal and his colleagues, Elsa Rossignol and Patrick Cossette of Universite de Montréal and Berge Minassian of the University of Toronto.
The team identified eight new genes involved in this type of epilepsy thanks to their use of whole-genome sequencing, which had never been done before in an epileptic study of this scope. The results of their study were recently published in the American Journal of Human Genetics. The researchers have identified a causal link between Developmental and Epileptic Encephalopathy (DEE) and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Developmental and epileptic encephalopathy (DEE) is a group of conditions characterised by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity.This discovery has further-reaching implications. In the context of epilepsy de novo mutations seem to involve mechanisms of gene disruption that are unlike those involved in intellectual disability. Mutations in epilepsy tend to affect specific areas of the gene, whereas mutations associated with intellectual disability are more often distributed throughout the entire gene.
Knowledge of these mechanisms of action is crucial for the development of personalised epilepsy treatments. However, much more work is needed before these treatments can be harmonised with patients' genetic profiles.
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic EncephalopathiesHamdan, Fadi F. et al.The American Journal of Human Genetics , Volume 101 , Issue 5 , 664 - 685