Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33561
Title: Familial mesial temporal lobe epilepsy: clinical spectrum and genetic evidence for a polygenic architecture.
Austin Authors: Harris, Rebekah V;Oliver, Karen L;Perucca, Piero ;Striano, Pasquale;Labate, Angelo;Riva, Antonella;Grinton, Bronwyn E;Reid, Joshua;Hutton, Jessica;Todaro, Marian;O'Brien, Terence J;Kwan, Patrick;Sadleir, Lynette G;Mullen, Saul A ;Dazzo, Emanuela;Crompton, Douglas E;Scheffer, Ingrid E ;Bahlo, Melanie;Nobile, Carlo;Gambardella, Antonio;Berkovic, Samuel F 
Affiliation: Epilepsy Research Centre
Population 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.
IRCCS Istituto Giannina Gaslini, member of ERN-Epicare, Genoa, Italy.
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Neurophysiopatology and Movement Disorders Clinic, University of Messina, Italy.
Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.;Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Departments 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.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.
Medicine (University of Melbourne)
Population 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.
Neuroscience Institute, National Research Council of Italy, Padua, Padova, Italy.
Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
Issue Date: Nov-2023
Date: 2023
Publication information: Annals of Neurology 2023-11; 94(5)
Abstract: Familial 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33561
DOI: 10.1002/ana.26765
ORCID: 0000-0002-2648-7828
0000-0002-7855-7066
0000-0002-8827-7324
0000-0001-9152-5571
0000-0002-2311-2174
0000-0001-7384-3074
0000-0003-4580-841X
Journal: Annals of Neurology
PubMed URL: 37597255
ISSN: 1531-8249
Type: Journal Article
Appears in Collections:Journal articles

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Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.