Journal article
Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy
S Khoshkhoo, Y Wang, Y Chahine, EZ Erson-Omay, SM Robert, E Kiziltug, EC Damisah, C Nelson-Williams, G Zhu, W Kong, AY Huang, E Stronge, HW Phillips, BH Chhouk, S Bizzotto, MH Chen, TN Adikari, Z Ye, T Witkowski, D Lai Show all
JAMA Neurology | AMER MEDICAL ASSOC | Published : 2023
Abstract
Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown. Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE. Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from ..
View full abstractRelated Projects (2)
Grants
Awarded by Horizon 2020 Framework Programme
Funding Acknowledgements
Dr Khoshkhoo was supported by grants R25-NS065743 and K08-NS128272 from the National Institutes of Health and a Doris Duke Physician Scientist Fellowship. Mr Stronge was supported by grant T32-GM007753 from the National Institutes of Health. Dr Phillips was supported by grant R25-NS079198 from the National Institutes of Health. Dr Bizzotto was supported by the Manton Center for Orphan Disease Research at Boston Children's Hospital and is supported by a European Commission's Horizon 2020 Research and Innovation Programme Marie Sklodowska-Curie Actions Individual Fellowship (grant agreement 101026484). Dr Scheffer was supported by Australia National Health and Medical Research Council Investigator Grant 1172897. Dr Berkovic was supported by Australia National Health and Medical Research Council Investigator Grant 1196637. Dr Hildebrand was supported by Australia National Health and Medical Research Council Ideas Grant 2012287. Drs Berkovic and Hildebrand were supported by Australia National Health and Medical Research Council Project Grants 1129054 and 1079058. Dr Yang was supported by grants R01-NS035129 and R01-NS094596 from the National Institutes of Health. Drs Heinzen, Lai, and some of the sequence data generation was supported by the grant R01-NS094596 from the National Institutes of Health. Dr Lee was supported by the Suh Kyungbae Foundation, National Institutes of Health grants DP2-AG072437 and R01-AG070921, and the Allen Discovery Center program. Dr Walsh was supported by grant R01-NS035129 from the National Institutes of Health and by the Allen Frontiers Program. Dr Walsh is an Investigator of the Howard Hughes Medical Institute. Dr Kahle was supported by the Yale-Rockefeller Centers for Mendelian Genomics, grants R01-NS109358, R01-NS111029, and R01-NS117609 from the National Institutes of Health, the Simons Foundation, March of Dimes, Hydrocephalus Association, and Rudi Schulte Research Institute.