Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33561
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dc.contributor.authorHarris, Rebekah V-
dc.contributor.authorOliver, Karen L-
dc.contributor.authorPerucca, Piero-
dc.contributor.authorStriano, Pasquale-
dc.contributor.authorLabate, Angelo-
dc.contributor.authorRiva, Antonella-
dc.contributor.authorGrinton, Bronwyn E-
dc.contributor.authorReid, Joshua-
dc.contributor.authorHutton, Jessica-
dc.contributor.authorTodaro, Marian-
dc.contributor.authorO'Brien, Terence J-
dc.contributor.authorKwan, Patrick-
dc.contributor.authorSadleir, Lynette G-
dc.contributor.authorMullen, Saul A-
dc.contributor.authorDazzo, Emanuela-
dc.contributor.authorCrompton, Douglas E-
dc.contributor.authorScheffer, Ingrid E-
dc.contributor.authorBahlo, Melanie-
dc.contributor.authorNobile, Carlo-
dc.contributor.authorGambardella, Antonio-
dc.contributor.authorBerkovic, Samuel F-
dc.date2023-
dc.date.accessioned2023-08-23T07:20:02Z-
dc.date.available2023-08-23T07:20:02Z-
dc.date.issued2023-11-
dc.identifier.citationAnnals of Neurology 2023-11; 94(5)en_US
dc.identifier.issn1531-8249-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/33561-
dc.description.abstractFamilial mesial temporal lobe epilepsy (FMTLE) is an important focal epilepsy syndrome; its molecular genetic basis is unknown. Clinical descriptions of FMTLE vary between a mild syndrome with prominent déjà vu to a more severe phenotype with febrile seizures and hippocampal sclerosis. We aimed to refine the phenotype of FMTLE by analyzing a large cohort and asked whether common risk variants for focal epilepsy and/or febrile seizures, measured by polygenic risk scores (PRS), are enriched in individuals with FMTLE. We studied 134 families with ≥2 first or second-degree relatives with temporal lobe epilepsy (TLE), with clear mesial ictal semiology required in at least one individual. PRS were calculated for 227 FMTLE cases, 124 unaffected relatives and 16,077 population controls. Age of FMTLE onset ranged from 2.5-70 years (median = 18, IQR = 13-28 years). The most common focal seizure symptom was déjà vu (62% of cases), followed by epigastric rising sensation (34%), and fear or anxiety (22%). The clinical spectrum included rare cases with drug-resistance and/or hippocampal sclerosis. FMTLE cases had a higher mean Focal Epilepsy PRS than population controls (OR 1.24, 95% CI 1.06, 1.46, p = 0.007); in contrast, no enrichment for the Febrile Seizure PRS was observed. FMTLE is a generally mild drug-responsive syndrome with déjà vu being the commonest symptom. In contrast to dominant monogenic focal epilepsy syndromes, our molecular data support a polygenic basis for FMTLE. Furthermore, the PRS data suggest that sub-genome-wide significant focal epilepsy GWAS SNPs are important risk variants for FMTLE. This article is protected by copyright. All rights reserved.en_US
dc.language.isoeng-
dc.titleFamilial mesial temporal lobe epilepsy: clinical spectrum and genetic evidence for a polygenic architecture.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleAnnals of Neurologyen_US
dc.identifier.affiliationEpilepsy Research Centreen_US
dc.identifier.affiliationPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.;Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.en_US
dc.identifier.affiliationIRCCS Istituto Giannina Gaslini, member of ERN-Epicare, Genoa, Italy.en_US
dc.identifier.affiliationDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.en_US
dc.identifier.affiliationNeurophysiopatology and Movement Disorders Clinic, University of Messina, Italy.en_US
dc.identifier.affiliationDepartment of Neurology, Alfred Health, Melbourne, Victoria, Australia.;Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.en_US
dc.identifier.affiliationDepartments of Medicine and Neurology, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Victoria, Australia.;Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.;Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.en_US
dc.identifier.affiliationDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.en_US
dc.identifier.affiliationDepartment of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.en_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.identifier.affiliationPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.;Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.en_US
dc.identifier.affiliationNeuroscience Institute, National Research Council of Italy, Padua, Padova, Italy.en_US
dc.identifier.affiliationInstitute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.en_US
dc.identifier.doi10.1002/ana.26765en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0002-2648-7828en_US
dc.identifier.orcid0000-0002-7855-7066en_US
dc.identifier.orcid0000-0002-8827-7324en_US
dc.identifier.orcid0000-0001-9152-5571en_US
dc.identifier.orcid0000-0002-2311-2174en_US
dc.identifier.orcid0000-0001-7384-3074en_US
dc.identifier.orcid0000-0003-4580-841Xen_US
dc.identifier.pubmedid37597255-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
crisitem.author.deptNeurology-
crisitem.author.deptComprehensive Epilepsy Program-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptNeurology-
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