Journal article

Contribution of rare genetic variants to drug response in absence epilepsy

Kenneth A Myers, Mark F Bennett, Bronwyn E Grinton, Gabriel Dabscheck, Eunice K Chan, Luis E Bello-Espinosa, Lynette G Sadleir, Sabrina D'Alfonso, Amy L Schneider, John A Damiano, Michael S Hildebrand, Melanie Bahlo, Samuel F Berkovic, Jeffrey Buchhalter, Ingrid E Scheffer

EPILEPSY RESEARCH | ELSEVIER | Published : 2021

Abstract

OBJECTIVE: We investigated the possible significance of rare genetic variants to response to valproic acid (VPA) and ethosuximide (ETX) in patients with absence epilepsy. Our primary hypothesis was that rare CACNA1H variants are more frequent in ETX-non-responsive patients compared to ETX-responsive. Our secondary hypothesis was that rare variants in GABA-receptor genes are more frequent in VPA-non-responsive patients compared to VPA-responsive. METHODS: We recruited patients with absence epilepsy treated with both VPA and ETX, and performed whole exome sequencing in order to investigate the potential role of rare variants in CACNA1H, other voltage-gated calcium channel (VGCC) genes, or GABA..

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Grants

Awarded by Citizens United for Research in Epilepsy Taking Flight Research Award


Awarded by Australian National Health and Medical Research Council Research Council (NHMRC)


Funding Acknowledgements

This work was primarily funded by Citizens United for Research in Epilepsy Taking Flight Research Award [grant number 439534] to KAM. Additional support from Australian National Health and Medical Research Council Research Council (NHMRC) Program Grant 1091593 to IES and SFB, and Senior Practitioner Fellowship1104831 to IES. Additional support from Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (MFB and MB). The funding sources had no role in the collection, analysis or interpretation of data; or in the writing of the report; or in the decision to submit the article for publication.