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Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model

Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnorm...

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Autores principales: Douaud, Marine, Feve, Katia, Pituello, Fabienne, Gourichon, David, Boitard, Simon, Leguern, Eric, Coquerelle, Gérard, Vieaud, Agathe, Batini, Cesira, Naquet, Robert, Vignal, Alain, Tixier-Boichard, Michèle, Pitel, Frédérique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203167/
https://www.ncbi.nlm.nih.gov/pubmed/22046416
http://dx.doi.org/10.1371/journal.pone.0026932
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author Douaud, Marine
Feve, Katia
Pituello, Fabienne
Gourichon, David
Boitard, Simon
Leguern, Eric
Coquerelle, Gérard
Vieaud, Agathe
Batini, Cesira
Naquet, Robert
Vignal, Alain
Tixier-Boichard, Michèle
Pitel, Frédérique
author_facet Douaud, Marine
Feve, Katia
Pituello, Fabienne
Gourichon, David
Boitard, Simon
Leguern, Eric
Coquerelle, Gérard
Vieaud, Agathe
Batini, Cesira
Naquet, Robert
Vignal, Alain
Tixier-Boichard, Michèle
Pitel, Frédérique
author_sort Douaud, Marine
collection PubMed
description Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans.
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spelling pubmed-32031672011-11-01 Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model Douaud, Marine Feve, Katia Pituello, Fabienne Gourichon, David Boitard, Simon Leguern, Eric Coquerelle, Gérard Vieaud, Agathe Batini, Cesira Naquet, Robert Vignal, Alain Tixier-Boichard, Michèle Pitel, Frédérique PLoS One Research Article Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans. Public Library of Science 2011-10-27 /pmc/articles/PMC3203167/ /pubmed/22046416 http://dx.doi.org/10.1371/journal.pone.0026932 Text en Douaud et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Douaud, Marine
Feve, Katia
Pituello, Fabienne
Gourichon, David
Boitard, Simon
Leguern, Eric
Coquerelle, Gérard
Vieaud, Agathe
Batini, Cesira
Naquet, Robert
Vignal, Alain
Tixier-Boichard, Michèle
Pitel, Frédérique
Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model
title Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model
title_full Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model
title_fullStr Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model
title_full_unstemmed Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model
title_short Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model
title_sort epilepsy caused by an abnormal alternative splicing with dosage effect of the sv2a gene in a chicken model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203167/
https://www.ncbi.nlm.nih.gov/pubmed/22046416
http://dx.doi.org/10.1371/journal.pone.0026932
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