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Genetic involvement in epilepsy?

A gene involved in so-called “focal” epilepsy, the most frequent form of the condition, has been discovered by the research team directed by Eric Leguern and Stéphanie Baulac of  Inserm unit 975 “Genetics and physiopathology of family epilepsy” at the Institut du Cerveau et de la Moelle (ICM) of the Pitié-Salpêtrière Hospital. The researchers studied families in which the affected members presented with various focal epilepsy syndromes. In 37% of families, mutations were found in a shared gene. This discovery makes it possible to envisage new mechanisms that should help to produce a better understanding of the condition. The results of the study were published in a letter in the journal Nature Genetics dated 31 March 2013.

Focal epilepsy represents nearly 70% of all epilepsies. Of these, several family syndromes were identified and characterised by the epileptogenic focus of the attacks, namely dominant autosomic nocturnal frontal epilepsy, temporal lobe family epilepsy and variable-focus family epilepsy.

Thanks to the clinical characterisation of 16 families, in collaboration with clinicians at the Strasbourg University Hospitals, researchers have just discovered an important gene involved in several forms of family focal epilepsy. The high-speed DNA sequencing technique makes it possible to identify a mutation that introduces a mismatch with the reading of the DEPDC5 gene (DEP domain containing protein 5) which codes for a protein whose function is still unknown. The subsequent high-speed sequencing of the gene revealed the presence of mutations in six families of the cohort out of 16, i.e. more than one third. The high frequency of mutations in the DEPDC5 gene would seem to presage favourable outcomes for patients and families in terms of molecular and clinical diagnosis.

“The identification of mutations in families whose members suffer from frontal, temporal  or variable focal epilepsy shows that this gene is a common denominator in epileptic syndromes long considered to be unrelated, due to the fact that the focus was found to be in different parts of the brain and the electro-clinical expression observed during attacks also being different”

, explains Stéphanie Baulac, Inserm head of research. “ These results suggest for the first time that the site that initiates the attacks is dissociated from the molecular cause”.

This discovery will make it possible to embark on new pathways to a better understanding of the pathological mechanisms of epilepsy for the development of new therapeutic targets, focal epilepsy being one of the most pharmaco-resistant conditions.

These research projects benefited from finance from the Institut Hospitalo-Universitaire IHU-A-ICM  in its “Investments for the future” initiative.

Photo: ©Inserm / L.Peris

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Researcher Contact

Stéphanie Baulac
Chargée de recherche Inserm

Unité 975 “Centre de recherche en neurosciences de la Pitié-Salpétrière”
Equipe “génétique des affections du système nerveux périphérique et de l’épilepsie”
01 57 27 43 39


Mutations of DEPDC5 cause autosomal dominant focal epilepsies

Saeko Ishida1,2, Fabienne Picard3, Gabrielle Rudolf4,5, Eric Noé1,2, Guillaume Achaz2,6,7, Pierre Thomas8,Pierre Genton9,10, Emeline Mundwiller11, Markus Wolff12, Christian Marescaux4, Richard Miles1,2, Michel Baulac1,2,13, Edouard Hirsch4, Eric Leguern1,2,14 & Stéphanie Baulac1,2

1 Institut National de la Santé et de la Recherche Médicale (INSERM) U975, ICM, Hôpital Pitié-Salpêtrière, Paris, France.
2 Université Pierre et Marie Curie–Paris 6 (UPMC), Paris, France.
3 Department of Neurology, University Hospitals of Geneva (HUG), Geneva, Switzerland. 4Neurology Department, Strasbourg University Hospital, Strasbourg, France.
5 Strasbourg University (UDS), Strasbourg, France.
6 Unité Mixte de Recherche (UMR) 7138, Centre National de la Recherche Scientifique (CNRS), Paris, France.
7 UMR 7241, Collège de France, Paris, France.
8 Service de Neurologie, Hôpital Pasteur, Nice, France.
9 Centre Saint Paul, Henri Gastaut, Marseille, France.
10 Mediterranean Institute of Neurobiology (INMED), Marseille, France.
11 Genotyping/Sequencing Platform of ICM, Hôpital Pitié-Salpêtrière, Paris, France.
12 Department of Paediatric Neurology University, Children’s Hospital, Tuebingen, Germany. 13 Epilepsy Unit, Assistance Publique–Hôpitaux de Paris (AP-HP) Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
14 Département de Génétique et de Cytogénétique, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Nature Genetics