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dc.contributor.authorDibbens, LM
dc.contributor.authorEkberg, J
dc.contributor.authorTaylor, I
dc.contributor.authorHodgson, BL
dc.contributor.authorConroy, S-J
dc.contributor.authorLensink, IL
dc.contributor.authorKumar, S
dc.contributor.authorZielinski, MA
dc.contributor.authorHarkin, LA
dc.contributor.authorSutherland, GR
dc.contributor.authorAdams, DJ
dc.contributor.authorBerkovic, SF
dc.contributor.authorScheffer, IE
dc.contributor.authorMulley, JC
dc.contributor.authorPoronnik, P
dc.date.accessioned2017-05-03T16:58:38Z
dc.date.available2017-05-03T16:58:38Z
dc.date.issued2007
dc.date.modified2010-01-07T02:17:58Z
dc.identifier.issn1601-1848
dc.identifier.doi10.1111/j.1601-183X.2007.00305.x
dc.identifier.urihttp://hdl.handle.net/10072/28099
dc.description.abstractPhotosensitive seizures occur most commonly in childhood and adolescence, usually as a manifestation of complex idiopathic generalized epilepsies (IGEs). Molecular mechanisms underlying this condition are yet to be determined because no susceptibility genes have been identified. The NEDD4-2 (Neuronally Expressed Developmentally Downregulated 4) gene encodes a ubiquitin protein ligase proposed to regulate cell surface levels of several ion channels, receptors and transporters involved in regulating neuronal excitability, including voltage-gated sodium channels (VGSCs), the most clinically relevant of the epilepsy genes. The regulation of NEDD4-2 in vivo involves complex interactions with accessory proteins in a cell type specific manner. We screened NEDD4-2 for mutations in a cohort of 253 families with IGEs. We identified three NEDD4-2 missense changes in highly conserved residues; S233L, E271A and H515P in families with photosensitive generalized epilepsy. The NEDD4-2 variants were as effective as wild-type NEDD4-2 in downregulating the VGSC subtype Nav1.2 when assessed in the Xenopus oocyte heterologous expression system showing that the direct interaction with the ion channel was not altered by these variants. These data raise the possibility that photosensitive epilepsy may arise from defective interaction of NEDD4-2 with as yet unidentified accessory or target proteins.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBlackwell
dc.publisher.placeDenmark
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom750
dc.relation.ispartofpageto755
dc.relation.ispartofissue8
dc.relation.ispartofjournalGenes, Brain and Behavior
dc.relation.ispartofvolume6
dc.rights.retentionY
dc.subject.fieldofresearchCell Neurochemistry
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchPsychology and Cognitive Sciences
dc.subject.fieldofresearchcode060105
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode11
dc.subject.fieldofresearchcode17
dc.titleNEDD4-2 as a potential candidate susceptibility gene for epileptic photosensitivity
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2007
gro.hasfulltextNo Full Text
gro.griffith.authorEkberg, Jenny A.


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