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Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

2013-09-06Journal article Open access
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dc.contributor.authorKasperavičiute, D.
dc.contributor.authorCatarino, C.B.
dc.contributor.authorMatarin, M.
dc.contributor.authorLeu, C.
dc.contributor.authorNovy, J.
dc.contributor.authorTostevin, A.
dc.contributor.authorLeal, B.
dc.contributor.authorHessel, E.V.S.
dc.contributor.authorHallmann, K.
dc.contributor.authorHildebrand, M.S.
dc.contributor.authorDahl, H-H.M.
dc.contributor.authorRyten, M.
dc.contributor.authorTrabzuni, D.
dc.contributor.authorRamasamy, A.
dc.contributor.authorAlhusaini, S.
dc.contributor.authorDoherty, C.P.
dc.contributor.authorDorn, T.
dc.contributor.authorHansen, J.
dc.contributor.authorKrämer, G.
dc.contributor.authorSteinhoff, B.J.
dc.contributor.authorZumsteg, D.
dc.contributor.authorDuncan, S.
dc.contributor.authorKälviäinen, R.K.
dc.contributor.authorEriksson, K.J.
dc.contributor.authorKantanen, A-M
dc.contributor.authorPandolfo, M.
dc.contributor.authorGruber-Sedlmayr, U.
dc.contributor.authorSchlachter, K.
dc.contributor.authorReinthaler, E.M.
dc.contributor.authorStogmann, E.
dc.contributor.authorZimprich, F.
dc.contributor.authorTheatre, E.
dc.contributor.authorSmith, C.
dc.contributor.authorObrien, T.J.
dc.contributor.authorTan, K.M.
dc.contributor.authorPetrovski, S.
dc.contributor.authorRobbiano, A.
dc.contributor.authorParavidino, R.
dc.contributor.authorZara, F.
dc.contributor.authorStriano, P.
dc.contributor.authorSperling, M.R.
dc.contributor.authorBuono, R.J.
dc.contributor.authorHakonarson, H.
dc.contributor.authorChaves, J.
dc.contributor.authorCosta, P.P.
dc.contributor.authorSilva, B.M.
dc.contributor.authorDa Silva, A.M.
dc.contributor.authorDe Graan, P.N.E.
dc.contributor.authorKoeleman, B.P.C.
dc.contributor.authorBecker, A.
dc.contributor.authorSchoch, S.
dc.contributor.authorVon Lehe, M.
dc.contributor.authorReif, P.S.
dc.contributor.authorRosenow, F.
dc.contributor.authorBecker, F.
dc.contributor.authorWeber, Y.
dc.contributor.authorLerche, H.
dc.contributor.authorRoessler, K.
dc.contributor.authorBuchfelder, M.
dc.contributor.authorHamer, H.M.
dc.contributor.authorKobow, K.
dc.contributor.authorCoras, R.
dc.contributor.authorBlumcke, I.
dc.contributor.authorScheffer, I.E.
dc.contributor.authorBerkovic, S.F.
dc.contributor.authorWeale, M.E.
dc.contributor.authorDelanty, N.
dc.contributor.authorDepondt, C.
dc.contributor.authorCavalleri, G.L.
dc.contributor.authorKunz, W.S.
dc.contributor.authorSisodiya, S.M.
dc.date.accessioned2014-03-31T16:18:30Z
dc.date.available2014-03-31T16:18:30Z
dc.date.issued2013-09-06
dc.description.abstractEpilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.por
dc.identifier.citationBrain. 2013 Oct;136(Pt 10):3140-50. doi: 10.1093/brain/awt233. Epub 2013 Sep 6por
dc.identifier.issn0006-8950
dc.identifier.issndoi: 10.1093/brain/awt233
dc.identifier.urihttp://hdl.handle.net/10400.18/2206
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherOxford University Press (OUP)por
dc.relation.publisherversionhttp://brain.oxfordjournals.org/content/136/10/3140.longpor
dc.subjectEpilepsypor
dc.subjectHippocampal Sclerosispor
dc.subjectFebrile Seizurespor
dc.subjectMTLEpor
dc.subjectGWASpor
dc.subjectGenome Wide Association Studypor
dc.subjectSCN1Apor
dc.subjectComplex Disease Geneticspor
dc.subjectDeterminantes da Saúde e da Doençapor
dc.subjectDoenças Genéticas
dc.titleEpilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1Apor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage3150por
oaire.citation.startPage3140por
oaire.citation.titleBrainpor
oaire.citation.volume136(10)por
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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