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: Marine Douaud, Katia Feve, Fabienne Pituello, David Gourichon, Simon Boitard, Eric Leguern, Gérard Coquerelle, Agathe Vieaud, Cesira Batini, Robert Naquet, Alain Vignal, Michèle Tixier-Boichard, Frédérique Pitel
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spelling oai:doaj.org-article:b80ba1a73f704c02900e8ff212a1d96e2021-11-18T07:35:34ZEpilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model.1932-620310.1371/journal.pone.0026932https://doaj.org/article/b80ba1a73f704c02900e8ff212a1d96e2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22046416/?tool=EBIhttps://doaj.org/toc/1932-6203Photosensitive 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.Marine DouaudKatia FeveFabienne PituelloDavid GourichonSimon BoitardEric LeguernGérard CoquerelleAgathe VieaudCesira BatiniRobert NaquetAlain VignalMichèle Tixier-BoichardFrédérique PitelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26932 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Marine Douaud
Katia Feve
Fabienne Pituello
David Gourichon
Simon Boitard
Eric Leguern
Gérard Coquerelle
Agathe Vieaud
Cesira Batini
Robert Naquet
Alain Vignal
Michèle Tixier-Boichard
Frédérique Pitel
Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model.
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.
format article
author Marine Douaud
Katia Feve
Fabienne Pituello
David Gourichon
Simon Boitard
Eric Leguern
Gérard Coquerelle
Agathe Vieaud
Cesira Batini
Robert Naquet
Alain Vignal
Michèle Tixier-Boichard
Frédérique Pitel
author_facet Marine Douaud
Katia Feve
Fabienne Pituello
David Gourichon
Simon Boitard
Eric Leguern
Gérard Coquerelle
Agathe Vieaud
Cesira Batini
Robert Naquet
Alain Vignal
Michèle Tixier-Boichard
Frédérique Pitel
author_sort Marine Douaud
title 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_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_sort epilepsy caused by an abnormal alternative splicing with dosage effect of the sv2a gene in a chicken model.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/b80ba1a73f704c02900e8ff212a1d96e
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