Genetic analysis is a promising avenue for better understanding the different forms of epilepsy. More than 100 genes linked to the disease have already been discovered.
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Today, to explain the genesis of epilepsies, a new avenue is being explored: genetics. As Rima Nabbout, neuropediatrician at the Necker-Enfants Malades hospital in Paris, explains, “it must be recognized that the advances are relatively recent because for a long time, we had a “classic” genetic approach. [en recherchant LE gène de l’épilepsie, NDLR], whereas it is more a question of genetic predispositions linked to one or more genes. In fact, there are epilepsies associated with a single gene, and others no doubt due to interactions between several genes and the environment.
More than 100 genes identified
“Currently, around a hundred genes have been identified, mainly for monogenic epilepsies”, indicates Éric Le Guern, geneticist at the ICM. Logically, “the first discoveries concerned the genes coding for ion channels and neurotransmitter receptors, major players in neuronal excitability”, adds the geneticist.
Thus, “80% of patients with Dravet syndrome, a severe and rare childhood epilepsy, have mutations in the SCN1A gene which codes for a sodium channel subunit and 60% of patients with partial onset seizures migrants have a mutation in the KCNT1 gene that codes for a potassium channel1 “says Rima Nabbout. In the same vein, Éric Le Guern’s team has associated abnormalities of another ion channel, HCN1, with an epileptic encephalopathy similar to Dravet syndrome.2.
Improve genetic counseling
However, epilepsies are not limited to channel and receptor abnormalities. “Genes involved in other cellular pathways are therefore beginning to be identified,” explains Éric Le Guern. This is the case of mutations in the DEPDC5 gene that Stéphanie Baulac of the ICM has identified in partial familial epilepsies, some of which present malformations of the cortex. This gene codes for a protein that regulates the mTOR pathway involved in particular in proliferation, mobility and cell survival. »
The hope of mapping the genes responsible for epilepsy – Stéphanie Baulac from ICM we Vimeo.
For physicians, the interest of identifying these genes is multiple. “This makes it possible to give a name to the disease, to stop the etiological research [des causes des maladies, NDLR] expensive and tedious for the child and the family, and makes it possible to offer genetic counseling when the parents wish, for example, to have other children, which is very important, underlines Rima Nabbout. It can also improve management and have an impact on treatment decisions. »
Francoise Dupuy Maury
Science&Santé, the Inserm magazine
1 – G.Barcia et al. Nature Genetics, 2012 Nov;44(11):1255-9
2 – C. Nava et al. Nature Genetics, 20 April 2014; 46: 640-5
3 – S.Baulac et al. Annals of Neurology, March 13, 2015; 77 (4): 675-8
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