Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16417
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dc.contributor.authorHildebrand, Michael S-
dc.contributor.authorPhillips, A Marie-
dc.contributor.authorMullen, Saul A-
dc.contributor.authorAdlard, Paul A-
dc.contributor.authorHardies, Katia-
dc.contributor.authorDamiano, John A-
dc.contributor.authorWimmer, Verena-
dc.contributor.authorBellows, Susannah T-
dc.contributor.authorMcMahon, Jacinta M-
dc.contributor.authorBurgess, Rosemary-
dc.contributor.authorHendrickx, Rik-
dc.contributor.authorWeckhuysen, Sarah-
dc.contributor.authorSuls, Arvid-
dc.contributor.authorDe Jonghe, Peter-
dc.contributor.authorScheffer, Ingrid E-
dc.contributor.authorPetrou, Steven-
dc.contributor.authorBerkovic, Samuel F-
dc.contributor.authorReid, Christopher A-
dc.date.accessioned2016-11-16T05:15:04Z-
dc.date.available2016-11-16T05:15:04Z-
dc.date.issued2015-12-09-
dc.identifier.citationScientific Reports 2016; 5: 17816en_US
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/16417-
dc.description.abstractFebrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn(2+)) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn(2+) homeostasis contributes to susceptibility is unknown. Synaptic Zn(2+) is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn(2+) into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn(2+) increases the risk of FS and more broadly support the idea that impaired synaptic Zn(2+) homeostasis can contribute to neuronal hyperexcitability.en_US
dc.subjectCation Transport Proteinsen_US
dc.subjectSeizures, Febrileen_US
dc.subjectZincen_US
dc.titleLoss of synaptic Zn2+ transporter function increases risk of febrile seizuresen_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleScientific Reportsen_US
dc.identifier.affiliationThe Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australiaen_US
dc.identifier.affiliationEpilepsy Research Centre, Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationSchool of Biosciences, University of Melbourne, Parkville, Victoria, Australiaen_US
dc.identifier.affiliationNeurogenetics Group, Department of Molecular Genetics, VIB, Belgiumen_US
dc.identifier.affiliationLaboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgiumen_US
dc.identifier.affiliationDivision of Neurology, Antwerp University Hospital, Antwerp, Belgiumen_US
dc.identifier.affiliationDepartment of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australiaen_US
dc.type.studyortrialCase Control Studiesen_US
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/26647834en_US
dc.identifier.doi10.1038/srep17816en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0002-2311-2174en_US
dc.identifier.orcid0000-0003-4580-841Xen_US
dc.type.austinJournal Articleen_US
local.name.researcherBerkovic, Samuel F
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptNeurology-
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