Heterogeneous contribution of microdeletions in the development of common generalized and focal epilepsies

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dc.catalogadordfo
dc.contributor.authorPérez-Palma, E.
dc.contributor.authorHelbig, I.
dc.contributor.authorKlein, K.M.
dc.contributor.authorAnttila, V.
dc.contributor.authorHorn, H.
dc.contributor.authorReinthaler, E.M.
dc.contributor.authorGormley, P.
dc.contributor.authorGanna, A.
dc.contributor.authorByrnes, A.
dc.contributor.authorPernhorst, K.
dc.contributor.authorToliat, M.R.
dc.contributor.authorSaarentaus, E.
dc.contributor.authorHowrigan, D.P.
dc.contributor.authorHoffman, P.
dc.contributor.authorMiquel Poblete, Juan Francisco
dc.contributor.authorde Ferrari, G.
dc.contributor.authorNürnberg, P.
dc.contributor.authorLerche, H.
dc.contributor.authorZimprich, F.
dc.contributor.authorNeubauer, B.A.
dc.contributor.authorBecker, A.J.
dc.contributor.authorRosenow, F.
dc.contributor.authorPerucca, E.
dc.contributor.authorZara, F.
dc.contributor.authorWeber, Y.G.
dc.contributor.authorLal, D.
dc.date.accessioned2024-08-09T17:08:33Z
dc.date.available2024-08-09T17:08:33Z
dc.date.issued2017
dc.description.abstractBackground: Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted. Methods: We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genomewide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls. Results: When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00x10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Subtype specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22x10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78x10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls. Conclusions: Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.
dc.fechaingreso.objetodigital2024-08-09
dc.fuente.origenORCID
dc.identifier.doi10.1101/131359
dc.identifier.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-85095626457&partnerID=MN8TOARS
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87400
dc.information.autorucEscuela de Medicina; Miquel Poblete Juan Francisco; 0000-0002-0526-4377; 72216
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final30
dc.pagina.inicio1
dc.rightsacceso abierto
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleHeterogeneous contribution of microdeletions in the development of common generalized and focal epilepsies
dc.typepreprint
sipa.codpersvinculados72216
sipa.trazabilidadORCID;2024-08-05
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