Linked Life Data

17331106

Source:http://linkedlifedata.com/resource/pubmed/id/17331106

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-11-5
pubmed:abstractText
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(v)1.2 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1601-1848
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
750-5
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17331106-Case-Control Studies, pubmed-meshheading:17331106-Chromosomes, Human, Pair 18, pubmed-meshheading:17331106-Cohort Studies, pubmed-meshheading:17331106-Endosomal Sorting Complexes Required for Transport, pubmed-meshheading:17331106-Epilepsy, Generalized, pubmed-meshheading:17331106-Epilepsy, Reflex, pubmed-meshheading:17331106-Female, pubmed-meshheading:17331106-Genetic Predisposition to Disease, pubmed-meshheading:17331106-Humans, pubmed-meshheading:17331106-Ion Channel Gating, pubmed-meshheading:17331106-Male, pubmed-meshheading:17331106-Mutation, Missense, pubmed-meshheading:17331106-Pedigree, pubmed-meshheading:17331106-Sequence Deletion, pubmed-meshheading:17331106-Sequence Homology, Amino Acid, pubmed-meshheading:17331106-Sodium Channels, pubmed-meshheading:17331106-Ubiquitin-Protein Ligases
pubmed:year
2007
pubmed:articleTitle
NEDD4-2 as a potential candidate susceptibility gene for epileptic photosensitivity.
pubmed:affiliation
Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, SA 5006, Australia. leanne.dibbens@cywhs.sa.gov.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't