Please use this identifier to cite or link to this item:
https://repository.monashhealth.org/monashhealthjspui/handle/1/31837
Title: | NEDD4-2 as a potential candidate susceptibility gene for epileptic photosensitivity. | Authors: | Kumar S.;Ekberg J.;Taylor I.;Hodgson B.L.;Conroy S.-J.;Lensink I.L.;Zielinski M.A.;Poronnik P.;Mulley J.C.;Scheffer I.E.;Berkovic S.F.;Adams D.J.;Sutherland G.R.;Harkin L.A.;Dibbens L.M. | Institution: | (Dibbens, Hodgson, Zielinski, Harkin, Sutherland, Mulley) Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, SA, Australia (Dibbens, Harkin, Sutherland) Department of Paediatrics, University of Adelaide, SA, Australia (Ekberg, Conroy, Adams, Poronnik) School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia (Taylor, Berkovic, Scheffer) Epilepsy Research Centre, Department of Neurology, Royal Children's Hospital, Melbourne, Vic., Australia (Lensink, Kumar) Department of Haematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia (Scheffer) Neurosciences, Monash Medical Centre, Melbourne, Vic., Australia (Mulley) Department of Molecular and Biomedical Science, University of Adelaide, SA, Australia (Dibbens) Department of Genetic Medicine, Women's and Children's Hospital, 72 King William St, North Adelaide, SA 5006, Australia | Issue Date: | 17-Oct-2012 | Copyright year: | 2007 | Publisher: | Blackwell Publishing Ltd (9600 Garsington Road, Oxford OX4 2XG, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Genes, Brain and Behavior. 6 (8) (pp 750-755), 2007. Date of Publication: November 2007. | Abstract: | Photosensitive 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 Na v1.2 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. © 2007 Blackwell Publishing Ltd. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1111/j.1601-183X.2007.00305.x | PubMed URL: | 17331106 [http://www.ncbi.nlm.nih.gov/pubmed/?term=17331106] | ISSN: | 1601-1848 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/31837 | Type: | Article | Subjects: | controlled study adolescent adult allele animal cell article cell specificity cell surface cell type child cohort analysis down regulation epilepsy gene gene mutation generalized epilepsy genetic regulation genetic screening *genetic susceptibility genetic variability heterologous expression human major clinical study nerve cell excitability nonhuman nucleotide sequence oocyte *photosensitive epilepsy priority journal protein function protein protein interaction Xenopus cell receptor/ec [Endogenous Compound] ion channel *ubiquitin protein ligase unclassified drug voltage gated sodium channel *Neuronally Expressed Developmentally Downregulated 4 gene *ubiquitin protein ligase NEDD4 2 voltage gated sodium channel Nav1.2 epilepsy gene gene mutation generalized epilepsy genetic regulation genetic screening *genetic susceptibility genetic variability heterologous expression human major clinical study nerve cell excitability nonhuman nucleotide sequence oocyte *photosensitive epilepsy priority journal protein function protein protein interaction article adolescent cell specificity Xenopus adult cell surface cell type child animal cell cohort analysis controlled study down regulation allele |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Articles |
Show full item record
Items in Monash Health Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.