Familial Mesial Temporal Lobe Epilepsy: Clinical Spectrum and Genetic Evidence for a Polygenic Architecture

RV Harris; KL Oliver; P Perucca; P Striano; A Labate; A Riva; BE Grinton; J Reid; J Hutton; M Todaro; TJ O'Brien; P Kwan; LG Sadleir; SA Mullen; E Dazzo; DE Crompton; IE Scheffer; M Bahlo; C Nobile; A Gambardella; SF Berkovic

Journal article

Familial Mesial Temporal Lobe Epilepsy: Clinical Spectrum and Genetic Evidence for a Polygenic Architecture

RV Harris, KL Oliver, P Perucca, P Striano, A Labate, A Riva, BE Grinton, J Reid, J Hutton, M Todaro, TJ O'Brien, P Kwan, LG Sadleir, SA Mullen, E Dazzo, DE Crompton, IE Scheffer, M Bahlo, C Nobile, A Gambardella Show all

Annals of Neurology | WILEY | Published : 2023

DOI: 10.1002/ana.26765

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Abstract

Objective: 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 of patients 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. Methods: We studied 134 families with ≥ 2 first or second-degree relatives with temporal lobe epilepsy, with clear mesial ictal semiology required in at lea..

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University of Melbourne Researchers

Rebekah Harris Author

Karen L Oliver Author

Piero Perucca Author

Bronwyn Grinton Author

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Awarded by Norman Beischer Medical Research Foundation

Funding Acknowledgements

This study was supported by National Health and Medical Research Council (NHMRC) of Australia with Investigator grants to I. E. Scheffer (1172897), S. F. Berkovic (1196637), M. Bahlo (1195236), and T. J. O'Brien (APP1176426). I. E. Scheffer, S. F. Berkovic, and T. J. O'Brien were supported by a NHMRC Synergy Grant (APP2010562). I. E Scheffer is further supported by a NHMRC Practitioner Fellowship (1006110). P. Perucca was supported by an NHMRC Early Career Fellowship (APP1163708), the Epilepsy Foundation, The University of Melbourne, Monash University, the Sir Weary Dunlop Medical Research Foundation, Brain Australia, and the Norman Beischer Medical Research Foundation. M. Bahlo was supported by the Australian State of Victoria's Government's Operational Infrastructure Support Program, and the NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS). P. Kwan was supported by the Australian Medical Research Future Fund (MRFF) Practitioner Fellowship (GNT1136427). K. L. Oliver was supported by the Australian Commonwealth Government and the University of Melbourne Australian Government Research Training Program Scholarship (APP533086). L. G. Sadleir and New Zealand families were funded by grants from the Health Research Council of New Zealand and Cure Kids. The Italian cohort work was supported by NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)-A Multiscale Integrated Approach to the Study of the Nervous System in Health and Disease (DN. 1553 11.10.2022). IRCCS "G. Gaslini" is a member of ERN-Epicare. This study was also funded by a grant from the Italian League Against Epilepsy. The QSKIN Study was supported by Grants (APP1185416, APP1073898, and APP1063061) from the NHMRC. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.