mTOR signaling pathway genes in focal epilepsies
Abstract
Focal epilepsies, where seizures initiate in spatially limited networks, are the most frequent epilepsy type, accounting for two-thirds of patients. Focal epilepsies have long been thought to be acquired disorders; several focal epilepsy syndromes are now proven to be (genetically heterogeneous) monogenic disorders. While earlier genetic studies have demonstrated a strong contribution of ion channel and neurotransmitter receptor genes, or synaptic secreted protein genes, later work has revealed a new class of genes encoding components of the mechanistic target of rapamycin (mTOR) signal transduction pathway. The mTOR pathway controls a myriad of biological processes among which cell growth and protein synthesis in response to several extracellular and intracellular. Recently, germline mutations have been found in genes encoding the components of the GATOR1 complex (DEPDC5, NPRL2, NPRL3), a repressor of mTORC1. These mutations are increasingly recognized as causing a wide and yet evolving spectrum of focal epilepsy syndromes, with and without cortical structural abnormalities (usually focal cortical dysplasia). Brain somatic mutations in the gene encoding mTOR (MTOR) have recently been linked to focal cortical dysplasia and other associated brain pathologies including hemimegalencephaly. This chapter reviews the genetics and neurobiology of DEPDC5, NPRL2, and NPRL3, and summarizes the clinical and molecular spectrum of GATOR1-related epilepsies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
KICSTOR plays a role in the GATOR1-dependent repression of mTORC1 signaling.
“Consistent with the notion that these abnormalities are associated with mTORC1 hyperactivation and GATOR1 inactivation (Baldassari et al., 2016; Baulac, 2016), KICSTOR clearly plays a role in the GATOR1-dependent repression of mTORC1 signaling.”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Baulac, 2016
Cites
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · see citing works
Blümcke, I., Thom, M., Aronica, E., Armstrong, D. D., Vinters, H. V., Palmini, A., Jacques, T. S., AVANZINI, G., Barkovich, A. J., Battaglia, G. S., et al. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02777.x · Cited by 1,746 · see citing works
Bar-Peled, L., Chantranupong, L., Cherniack, A. D., Chen, W. W., Ottina, K. A., Grabiner, B. C., Spear, E. D., Carter, S. L., Meyerson, M., & Sabatini, D. M. (2013) · Science · doi:10.1126/science.1232044 · Cited by 1,080 · see citing works
Somatic mutation, genomic variation, and neurological disease
Poduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. (2013) · Science · doi:10.1126/science.1237758 · Cited by 584 · see citing works
Lim, J. S., Kim, W.-I., Kang, H., Kim, S. H., Park, A. H., Park, E. K., Cho, Y., Kim, H. M., Kim, J. A., Kim, J. A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3824 · Cited by 524 · see citing works
Somatic mutations in cerebral cortical malformations
Jamuar, S. S., Lam, A.-T. N., Kircher, M., D’Gama, A. M., Wang, J., Barry, B. J., Zhang, X., Hill, R. S., Partlow, J. N., Rozzo, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1314432 · Cited by 392 · see citing works
Mutations in DEPDC5 cause familial focal epilepsy with variable foci
Dibbens, L. M., de Vries, B., Donatello, S., Heron, S. E., Hodgson, B. L., Chintawar, S., Crompton, D. E., Hughes, J. N., Bellows, S. T., Klein, K. M., et al. (2013) · Nature Genetics · doi:10.1038/ng.2599 · Cited by 373 · see citing works
Panchaud, N., Gulli, M., & VIRGILIO, C. D. (2013) · Science Signaling · doi:10.1126/scisignal.2004112 · Cited by 290 · see citing works
D’Gama, A. M., Geng, Y., Couto, J. A., Martin, B., Boyle, E. A., LaCoursiere, C. M., Hossain, A. A., Hatem, N. E., Barry, B. J., Kwiatkowski, D. J., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24357 · Cited by 290 · see citing works
Bagnall, R. D., Crompton, D. E., Petrovski, S., Lam, L., Cutmore, C., Garry, S. I., Sadleir, L. G., Dibbens, L. M., Cairns, A. G., Kivity, S., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24596 · Cited by 283 · see citing works
Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations
Baulac, S., Ishida, S., Marsan, E., Miquel, C., Biraben, A., Nguyen, D., Nordli, D., Cossette, P., Nguyen, S., Lambrecq, V., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24368 · Cited by 279 · see citing works
Self-citationMutations of DEPDC5 cause autosomal dominant focal epilepsies
Ishida, S., Picard, F., Rudolf, G., Noé, E., Achaz, G., Thomas, P., Genton, P., Mundwiller, E., Wolff, M., Marescaux, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2601 · Cited by 269 · see citing works
Self-citationmTOR cascade activation distinguishes tubers from focal cortical dysplasia
Baybis, M., Yu, J., Lee, A., Golden, J. A., Weiner, H. L., McKhann, G. M., Aronica, E., & Crino, P. B. (2004) · Annals of Neurology · doi:10.1002/ana.20211 · Cited by 255 · see citing works
Ricos, M. G., Hodgson, B. L., Pippucci, T., Saidin, A., Ong, Y. S., Heron, S. E., Licchetta, L., Bisulli, F., Bayly, M. A., Hughes, J., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24547 · Cited by 246 · see citing works
Scheffer, I., Heron, S., Regan, B. M., Mandelstam, S., Crompton, D., Hodgson, B., Licchetta, L., Provini, F., Bisulli, F., Vadlamudi, L., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24126 · Cited by 228 · see citing works
LaSarge, C. L., & Danzer, S. C. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00018 · Cited by 193 · see citing works
Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb
Nakashima, M., Saitsu, H., Takei, N., Tohyama, J., Kato, M., Kitaura, H., Shiina, M., Shirozu, H., Masuda, H., Watanabe, K., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24444 · Cited by 184 · see citing works
Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia
Weckhuysen, S., Marsan, E., Lambrecq, V., Marchal, C., Morin‐Brureau, M., An-Gourfinkel, I., Baulac, M., Fohlen, M., Zetchi, C. K., Seeck, M., et al. (2016) · Epilepsia · doi:10.1111/epi.13391 · Cited by 181 · see citing works
Self-citationSudden unexpected death in epilepsy
Surges, R., & Sander, J. W. A. S. (2012) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283506714 · Cited by 171 · see citing works
Insulin signaling pathways in cortical dysplasia and TSC‐tubers: Tissue microarray analysis
Miyata, H., Chiang, A., & Vinters, H. V. (2004) · Annals of Neurology · doi:10.1002/ana.20234 · Cited by 152 · see citing works
Focal cortical dysplasia type II: biological features and clinical perspectives
Sisodiya, S. M., Fauser, S., Cross, J. H., & Thom, M. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70201-7 · Cited by 150 · see citing works
DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy
Picard, F., Makrythanasis, P., Navarro, V., Ishida, S., de Bellescize, J., Ville, D., Weckhuysen, S., Fosselle, E., Suls, A., de Jonghe, P., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000488 · Cited by 142 · see citing works
Self-citationFamilial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3
Sim, J. C. H., Scerri, T., Fanjul-Fernández, M., Riseley, J. R., Gillies, G., Pope, K., van Roozendaal, H., Heng, J., Mandelstam, S., McGillivray, G., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24502 · Cited by 135 · see citing works
Mechanistic Target of Rapamycin (mTOR) in Tuberous Sclerosis Complex-Associated Epilepsy
Curatolo, P. (2014) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2014.10.028 · Cited by 132 · see citing works
DEPDC5 mutations in genetic focal epilepsies of childhood
Lal, D., Reinthaler, E., Schubert, J., Muhle, H., Riesch, E., Kluger, G., Jabbari, K., Kawalia, A., Baumel, C., Holthausen, H., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24127 · Cited by 120 · see citing works
Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5
Scerri, T., Riseley, J. R., Gillies, G., Pope, K., Burgess, R., Mandelstam, S., Dibbens, L., Chow, C., Maixner, W., Harvey, A., et al. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.191 · Cited by 101 · see citing works
Focal malformations of cortical development: New vistas for molecular pathogenesis
Lim, K., & Crino, P. B. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.037 · Cited by 95 · see citing works
Depdc5 knockout rat: A novel model of mTORopathy.
Marsan, E., Ishida, S., Schramm, A. E., Weckhuysen, S., Muraca, G., Lecas, S., Liang, N., Treins, C., Pende, M., Roussel, D., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.02.010 · Cited by 95 · see citing works
Self-citationMolecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway*
Algret, R., Fernandez-Martinez, J., Shi, Y., Kim, S. J., Pellarin, R., Cimermancic, P., Cochet, E., Sali, A., Chait, B., Rout, M., et al. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.039388 · Cited by 84 · see citing works
Epileptic spasms are a feature of <i>DEPDC5</i> mTORopathy
Carvill, G. L., Crompton, D. E., Regan, B. M., McMahon, J. M., Saykally, J., Zemel, M., Schneider, A. L., Dibbens, L., Howell, K. B., Mandelstam, S., et al. (2015) · Neurology Genetics · doi:10.1212/nxg.0000000000000016 · Cited by 76 · see citing works
SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway
Dokudovskaya, S., & Rout, M. P. (2015) · Journal of Cell Science · doi:10.1242/jcs.168922 · Cited by 70 · see citing works
Two definite cases of sudden unexpected death in epilepsy in a family with a DEPDC5 mutation
Nascimento, F. A., Borlot, F., Cossette, P., Minassian, B. A., & Andrade, D. M. (2015) · Neurology Genetics · doi:10.1212/nxg.0000000000000028 · Cited by 64 · see citing works
Epilepsy with auditory features
Pippucci, T., Licchetta, L., Baldassari, S., Palombo, F., Menghi, V., D’Aurizio, R., Leta, C., Stipa, C., Boero, G., d’Orsi, G., et al. (2015) · Neurology Genetics · doi:10.1212/nxg.0000000000000005 · Cited by 60 · see citing works
Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR 1 complex gene NPRL 3
Korenke, G. C., Eggert, M., Thiele, H., Nürnberg, P., Sander, T., & Steinlein, O. K. (2016) · Epilepsia · doi:10.1111/epi.13307 · Cited by 60 · see citing works
Brain somatic mutations: the dark matter of psychiatric genetics?
Insel, T. R. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.168 · Cited by 56 · see citing works
DEPDC 5 mutations are not a frequent cause of familial temporal lobe epilepsy
Striano, P., Serioli, E., Santulli, L., Manna, I., Labate, A., Dazzo, E., Pasini, E., Gambardella, A., Michelucci, R., Striano, S., et al. (2015) · Epilepsia · doi:10.1111/epi.13094 · Cited by 46 · see citing works
A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French‐Canadian population
Martin, C., Meloche, C., Rioux, M., Nguyen, D., Carmant, L., Andermann, E., Gravel, M., & Cossette, P. (2014) · Clinical Genetics · doi:10.1111/cge.12311 · Cited by 46 · see citing works
Regulation of Hematopoiesis and Methionine Homeostasis by mTORC1 Inhibitor NPRL2
Dutchak, P. A., Laxman, S., Estill, S., Wang, C.-S., Wang, Y., Wang, Y.-G., Bulut, G. B., Gao, J.-M., Huang, L., & Tu, B. P. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.042 · Cited by 44 · see citing works
Nprl3 is required for normal development of the cardiovascular system
Kowalczyk, M. S., Hughes, J. R., Babbs, C., Sánchez‐Pulido, L., Szumska, D., Sharpe, J. A., Sloane-Stanley, J. A., Morriss‐Kay, G. M., Smoot, L. B., Roberts, A. E., et al. (2012) · Mammalian Genome · doi:10.1007/s00335-012-9398-y · Cited by 43 · see citing works
Genetics advances in autosomal dominant focal epilepsies: focus on DEPDC5.
Baulac, S. (2014) · Progress in Brain Research · doi:10.1016/b978-0-444-63326-2.00007-7 · Cited by 35 · see citing works
Self-citationvan Kranenburg, M., Hoogeveen-Westerveld, M., & Nellist, M. (2015) · Human Mutation · doi:10.1002/humu.22723 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neurodevelopmental Disorders: From Genetics to Functional Pathways
Parenti, I., Rabaneda, L. G., Schoen, H., & Novarino, G. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.004 · Cited by 634 · see citing works
KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1
Wolfson, R. L., Chantranupong, L., Wyant, G., Gu, X., Orozco, J. M., Shen, K., Condon, K. J., Petri, S., Kedir, J. F., Scaria, S. M., et al. (2017) · Nature · doi:10.1038/nature21423 · Cited by 308 · see citing works
Genomic diagnosis for children with intellectual disability and/or developmental delay
Bowling, K. M., Thompson, M. L., Amaral, M. D., Finnila, C. R., Hiatt, S. M., Engel, K. L., Cochran, J. N., Brothers, K. B., East, K. M., Gray, D. E., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0433-1 · Cited by 273 · see citing works
Ribierre, T., Deleuze, C., Bacq, A., Baldassari, S., Marsan, E., Chipaux, M., Muraca, G., Roussel, D., Navarro, V., Leguern, E., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99384 · Cited by 241 · see citing works
Self-citationThe landscape of epilepsy-related GATOR1 variants
Baldassari, S., Picard, F., Verbeek, N., van Kempen, M., Brilstra, E., Lesca, G., Conti, V., Guerrini, R., Bisulli, F., Licchetta, L., et al. (2018) · Genetics in Medicine · doi:10.1038/s41436-018-0060-2 · Cited by 216 · see citing works
Self-citationPerucca, P., Bahlo, M., & Berkovic, S. F. (2020) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120219-074937 · Cited by 235 · see citing works
Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum
Guerrini, R., Conti, V., Mantegazza, M., Balestrini, S., Galanopoulou, A. S., & Benfenati, F. (2023) · Physiological Reviews · doi:10.1152/physrev.00063.2021 · Cited by 196 · see citing works
Najm, I., Sarnat, H. B., & Blümcke, I. (2018) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12462 · Cited by 196 · see citing works
Review: Mechanistic target of rapamycin (mTOR) pathway, focal cortical dysplasia and epilepsy
Marsan, E., & Baulac, S. (2018) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12463 · Cited by 162 · see citing works
Self-citationGermline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy
Møller, R., Weckhuysen, S., Chipaux, M., Marsan, E., Taly, V., Bebin, E., Hiatt, S., Prokop, J., Bowling, K. M., Mei, D., et al. (2016) · Neurology: Genetics · doi:10.1212/nxg.0000000000000118 · Cited by 138 · see citing works
Self-citationG3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling
Prentzell, M. T., Rehbein, U., Sandoval, M. C., Meulemeester, A. D., Baumeister, R., Brohée, L., Berdel, B., Bockwoldt, M., Carroll, B., Chowdhury, S. R., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.024 · Cited by 148 · see citing works
Epilepsy in the mTORopathies: opportunities for precision medicine
Moloney, P. B., Cavalleri, G. L., & Delanty, N. (2021) · Brain Communications · doi:10.1093/braincomms/fcab222 · Cited by 126 · see citing works
Current Approaches and Future Directions for the Treatment of mTORopathies
Karalis, V., & Bateup, H. S. (2021) · Developmental Neuroscience · doi:10.1159/000515672 · Cited by 67 · see citing works
The Neurodevelopmental Pathogenesis of Tuberous Sclerosis Complex (TSC)
Feliciano, D. M. (2020) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2020.00039 · Cited by 69 · see citing works
Marmiesse, A. F., Roca, I., Díaz-Flores, F., Cantarín, V., Pérez-Poyato, M. S., Fontalba, A., Laranjeira, F., Quintans, S., Moldovan, O., Felgueroso, B., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01135 · Cited by 64 · see citing works
Neurodegenerative pathways as targets for acquired epilepsy therapy development
Casillas-Espinosa, P. M., Ali, I. Y., & O'Brien, T. J. (2020) · Epilepsia Open · doi:10.1002/epi4.12386 · Cited by 58 · see citing works
DEPDC5-related epilepsy: A comprehensive review.
Samanta, D. (2022) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2022.108678 · Cited by 52 · see citing works
Depdc5 knockdown causes mTOR‐dependent motor hyperactivity in zebrafish
de Calbiac, H., Dăbâcan, A., Marsan, E., Tostivint, H., Devienne, G., Ishida, S., Leguern, E., Baulac, S., Muresan, R., Kabashi, E., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.542 · Cited by 50 · see citing works
Self-citationDawson, R. E., Guil, A. N. N., Robertson, L., Piltz, S. G., Hughes, J. N., & Thomas, P. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104640 · Cited by 42 · see citing works
DEPDC5 as a potential therapeutic target for epilepsy
Myers, K., & Scheffer, I. (2017) · Expert opinion on therapeutic targets · doi:10.1080/14728222.2017.1316715 · Cited by 40 · see citing works
Pharmacogenetics of Drug-Resistant Epilepsy (Review of Literature)
Smolarz, B., Makowska, M., & Romanowicz, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111696 · Cited by 37 · see citing works
DEPDC5 mutations in familial and sporadic focal epilepsy
Tsai, M.-H., Chan, C.-K., Chang, Y., Yu, Y.-T., Chuang, S., Fan, W., Li, S.-C., Fu, T.-Y., Chang, W.-N., Liou, C., et al. (2017) · Clinical Genetics · doi:10.1111/cge.12992 · Cited by 39 · see citing works
Iffland, P. H., Baybis, M., Barnes, A. E., Leventer, R., Lockhart, P., & Crino, P. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.02.013 · Cited by 33 · see citing works
Quantitative Measurement of Functional Activity of the PI3K Signaling Pathway in Cancer
van de Stolpe, A. (2019) · Cancers · doi:10.3390/cancers11030293 · Cited by 40 · see citing works
Genetics of Focal Epilepsies: What do we know and where are we Heading?
Perucca, P. (2018) · Epiliepsy currents/Epilepsy currents · doi:10.5698/1535-7597.18.6.356 · Cited by 39 · see citing works
Liu, L., Chen, Z.-R., Xu, H., Liu, D.-T., Mao, Y., Liu, H.-K., Liu, X.-R., Zhou, P., Lin, S.-M., Li, B., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00821 · Cited by 32 · see citing works
NPRL3 loss alters neuronal morphology, mTOR localization, cortical lamination and seizure threshold
Iffland, P. H., Everett, M. E., Cobb-Pitstick, K., Bowser, L. E., Barnes, A. E., Babus, J. K., Romanowski, A. J., Baybis, M., Elziny, S., Puffenberger, E. G., et al. (2022) · Brain · doi:10.1093/brain/awac044 · Cited by 37 · see citing works
mi R 147b: A novel key regulator of interleukin 1 beta‐mediated inflammation in human astrocytes
van Scheppingen, J., Mills, J. D., Zimmer, T. S., Broekaart, D. W. M., Iori, V., Bongaarts, A., Anink, J. J., Iyer, A. M., Korotkov, A., Jansen, F. E., et al. (2018) · Glia · doi:10.1002/glia.23302 · Cited by 35 · see citing works
Rossini, L., Villani, F. S., Granata, T., Tassi, L., Tringali, G., Cardinale, F., Aronica, E., Spreafico, R., & Garbelli, R. (2016) · Epilepsy Research · doi:10.1016/j.eplepsyres.2016.12.002 · Cited by 34 · see citing works
Mechanistic Target of Rapamycin Pathway in Epileptic Disorders
Kim, J., & Lee, J. H. (2019) · Journal of Korean Neurosurgical Society · doi:10.3340/jkns.2019.0027 · Cited by 32 · see citing works
Gitaí, D. L. G., dos Santos, Y. D. R., Upadhya, R., Kodali, M., Madhu, L. N., & Shetty, A. K. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01797-1 · Cited by 30 · see citing works
Genetic testing in children enrolled in epilepsy surgery program. A real-life study
Straka, B., Splítková, B., Vlčková, M., Tesner, P., Zůnová, H., Krsková, L., Koblížek, M., Kynčl, M., Maulisová, A., Bukačová, K., et al. (2023) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2023.09.009 · Cited by 25 · see citing works
Sahly, A. N., Whitney, R., Costain, G., Chau, V., Otsubo, H., Ochi, A., Donner, E., Cunningham, J., Jones, K. C., Widjaja, E., et al. (2023) · Seizure · doi:10.1016/j.seizure.2023.03.004 · Cited by 18 · see citing works
Caplan, R., Mefford, H. C., Berl, M. M., Chang, B. S., Lin, J. J., Mazarati, A. M., Fureman, B. E., & Dingledine, R. J. (2016) · Epiliepsy currents/Epilepsy currents · doi:10.5698/1535-7511-16.3.182 · Cited by 15 · see citing works
Zhang, J., Shen, Y.-J., Yang, Z.-Z., Yang, F., Li, Y., Yu, B., Chen, W.-L., & Gan, J. (2021) · Journal of Human Genetics · doi:10.1038/s10038-021-00969-z · Cited by 10 · see citing works
Chang, B. S., Krishnan, V., Dulla, C. G., Jetté, N., Marsh, E. D., Dacks, P. A., Whittemore, V., & Poduri, A. (2020) · Epiliepsy currents/Epilepsy currents · doi:10.1177/1535759719895280 · Cited by 14 · see citing works
Signal integration in the (m)TORC1 growth pathway
Ramlaul, K., & Aylett, C. H. S. (2018) · Frontiers in Biology · doi:10.1007/s11515-018-1501-7 · Cited by 12 · see citing works
Variants inCHRNB2andCHRNA4Identified in Patients with Insular Epilepsy
Cadieux‐Dion, M., Meneghini, S., Villa, C., Toffa, D. H., Wickström, R., Bouthillier, A., Sandvik, U., Gustavsson, B., Mohamed, I., Cossette, P., et al. (2020) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2020.126 · Cited by 12 · see citing works
Li, Y., Zhao, X., Wang, S., Xu, K., Zhao, X., Huang, S., & Zhu, S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.766354 · Cited by 11 · see citing works
mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node
Ritter, L. M., Annear, N. M. P., Baple, E., Ben-Chaabane, L. Y., Bodi, I., Brosson, L., Cadwgan, J., Coslett, B., Crosby, A. H., Davies, D., et al. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-03740-1 · Cited by 10 · see citing works
FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila
Zhou, Y., Guo, J., Wang, X.-Y., Cheng, Y., Guan, J., Barman, P., Sun, M.-A., Fu, Y., Wei, W.-H., Feng, C.-J., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03860-z · Cited by 8 · see citing works
mTOR pathway in familial focal epilepsies
Ribierre, T., & Baulac, S. (2016) · Oncotarget · doi:10.18632/oncotarget.14234 · Cited by 11 · see citing works
Self-citationTranscriptome analysis of a ring chromosome 20 patient cohort
Myers, K., Bennett, M., Hildebrand, M., Coleman, M., Zhou, G.-Y., Hollingsworth, G., Cairns, A. G., Riney, K., Berkovic, S., Bahlo, M., et al. (2020) · Epilepsia · doi:10.1111/epi.16766 · Cited by 8 · see citing works
Szekeres‐Paraczky, C., Szocsics, P., Erőss, L., Fabó, D., Mód, L., & Maglóczky, Z. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094746 · Cited by 10 · see citing works
Baulac, S., & Weckhuysen, S. (2016) · University of Washington, Seattle eBooks · Cited by 10 · see citing works
Self-citationNovel GATOR1 variants in focal epilepsy
Kovačević, M., Janković, M. Z., Branković, M., Milicevic, O. S., Novaković, I. V., Sokić, D. V., Ristić, A. J., Shamsani, J., & Vojvodić, N. M. (2023) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2023.109139 · Cited by 9 · see citing works
Loss of Leucyl-tRNA synthetase b leads to ILFS1-like symptoms in zebrafish
Wang, Z., Song, J., Luo, L., & Ma, J. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.09.133 · Cited by 9 · see citing works
Pathogenic genes implicated in sleep-related hypermotor epilepsy: a research progress update
Yang, Y., Tuo, J., Zhang, J., Xu, Z., & Luo, Z. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1416648 · Cited by 10 · see citing works
Translational control in neurovascular brain development
Chalkiadaki, K., Statoulla, E., Μάρκου, Μ., Bellou, S., Bagli, E., Fotsis, T., Murphy, C., & Gkogkas, C. G. (2021) · Royal Society Open Science · doi:10.1098/rsos.211088 · Cited by 6 · see citing works
Yang, D., Wang, J., Qin, Z., Feng, J., Mao, C., Chen, Y., Huang, X., & Ruan, Y. (2023) · Epilepsia Open · doi:10.1002/epi4.12856 · Cited by 6 · see citing works
Brown, M. N., Gibson, K. M., Schmidt, M. A., Walters, D. C., Arning, E., Bottiglieri, T., & Roullet, J. (2020) · JIMD Reports · doi:10.1002/jmd2.12151 · Cited by 5 · see citing works
Gap Activity TOward Rags 1 variants in Chinese people with sporadic drug‐resistant focal epilepsy
Xiong, W., Tang, L., Lu, L., Zhang, L., Xiao, Y., & Zhou, D. (2018) · Acta Neurologica Scandinavica · doi:10.1111/ane.13046 · Cited by 6 · see citing works
Sidhu, R. K., Maparu, K., & Aran, K. R. (2025) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2025.108556 · Cited by 5 · see citing works
Clinical and genetic features of GATOR1 complex-associated epilepsy
Yin, K., Lei, X.-X., Yan, Z.-F., Yang, Y.-J., Deng, Q.-Q., Lu, Q., Zhang, X., Wang, M.-Y., & Liu, Q. (2023) · Journal of Medical Genetics · doi:10.1136/jmg-2021-108364 · Cited by 6 · see citing works
Clinical phenotype and genotype of NPRL2-related epilepsy: Four cases reports and literature review
Zhang, H., Deng, J., Gao, Z., Wang, Y., Zhao, F. Q., Zhao, H., & Fang, F. (2023) · Seizure · doi:10.1016/j.seizure.2023.09.003 · Cited by 5 · see citing works
A novel variation in DEPDC5 causing familial focal epilepsy with variable foci
Wang, Y., Niu, W., Shi, H. S., Bao, X., Liu, Y., Lu, M., & Sun, Y. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1414259 · Cited by 4 · see citing works
Structures and Functions of the Human GATOR1 Complex
Ivanova, I., & Shen, K. (2024) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-58843-3_12 · Cited by 4 · see citing works
An overview of the value of mTOR inhibitors to the treatment of epilepsy: the evidence to date
Moloney, P. B., & Delanty, N. (2025) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2025.2462280 · Cited by 4 · see citing works
The influence of genetics on epilepsy syndromes in infancy and childhood
Yozawitz, E. G., & Moshé, S. L. (2022) · Acta Epileptologica · doi:10.1186/s42494-022-00110-3 · Cited by 3 · see citing works
Lu, G., Jiang, L., Huang, D., Rong, Y.-X., Li, Y., Wei, L.-X., Ning, Y., Huang, S.-F., Mo, S., Meng, F.-H., et al. (2021) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x16666211206150934 · Cited by 3 · see citing works
Feria-Romero, I. A., Reyes-Cuayahuitl, A., Sosa-Maldonado, J., Montes-Aparicio, A. V., Mares, D. R., Pérez‐Pérez, D., Grijalva, I., & Orozco-Suárez, S. A. (2023) · Gene · doi:10.1016/j.gene.2023.147565 · Cited by 3 · see citing works
Winczewska-Wiktor, A., Braszka, M., Harada-Laszlo, M., Badura-Stronka, M., Kaczmarek, I., Starczewska, M., Wencel-Warot, A., Steinborn, B., & Jamsheer, A. (2023) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2023.109535 · Cited by 3 · see citing works
Clinical concordance evaluation of the causality of sequence variantsPreprint
Zhou, P., He, N., Lin, Z.-J., Yan, L.-M., Wang, J., Bian, W., Meng, H., Shi, Y., Su, T., Liu, X., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3270536/v1 · Cited by 3 · see citing works
Hippocampal dentate granule cells in temporal lobe epilepsy: A morphometry and transcriptomic study
Twible, C., Abdo, R., Zhao, C., & Zhang, Q. (2024) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.13008 · Cited by 2 · see citing works
Zhao, T., Chen, F., Cao, B., Yang, L., Yin, J., Li, Y., & Feng, F. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1595667 · Cited by 2 · see citing works
Neue Entwicklungen in der genetischen Grundlage kortikaler Malformationen
Döring, J. H., & Syrbe, S. (2019) · Clinical Epileptology · doi:10.1007/s10309-019-0266-6 · Cited by 2 · see citing works
Jansen, L. (2018) · Epilepsy Currents · doi:10.5698/1535-7597.18.3.197 · Cited by 2 · see citing works
Baer, S., Abi‐Warde, M., Spitz, M., Gauer, L., Hirsch, É., Laugel, V., Hirsch, M. P. V., Lambert, C., Piton, A., Schluth‐Bolard, C., et al. (2025) · Seizure · doi:10.1016/j.seizure.2025.03.013 · Cited by 1 · see citing works
Burani, M., Giovannini, G., Orlandi, N., Pugnaghi, M., Affronte, L., Malerba, M., Taruffi, L., Madrassi, L., Scolastico, S., Ballerini, A., et al. (2025) · Epilepsia · doi:10.1111/epi.18646 · Cited by 1 · see citing works
Clinical concordance evaluation of the causality of sequence variantsPreprint
Zhou, P., He, N., Lin, Z.-J., Yan, L.-M., Luo, S., Li, B., Wang, J., Bian, W., Meng, H., Shi, Y., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3270536/v2 · Cited by 1 · see citing works
Pineau, L., Buhler, E., Tarhini, S., Bauer, Š., Crépel, V., Françoise Watrin, A., Cardoso, C., Represa, A., Szepetowski, P., & Burnashev, N. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.01.569539 · Cited by 1 · see citing works
GATOR1 gene variants in focal epilepsy
Kovačević, M., Vojvodić, N. M., & Novaković, I. (2024) · Medicinski Podmladak · doi:10.5937/mp75-45140
DEPDC5-Related Familial Focal Epilepsy With Variable Foci-1: A Report of a Rare Case
Itani, A., Banjade, P., Shrestha, U., Surani, S., & Sharma, M. (2025) · Cureus · doi:10.7759/cureus.84627
Wang, S., Li, H., Zhao, X., Li, T., & Zhang, L. (2025) · Research Square · doi:10.21203/rs.3.rs-7874206/v1
de Calbiac, H. (2019) · theses.fr (ABES) · doi:10.70675/bafe951fz8332z4b0azb55bzac8a4af1955b
Cortical organoid model of DEPDC5-related focal cortical dysplasia and epilepsy
Maletić, M. (2022) · theses.fr (ABES) · doi:10.70675/ce51a4c6zec09z49b3z8571zd518d7fa745c
Pineau, L. (2023) · theses.fr (ABES) · doi:10.70675/39c790cfzdf57z416bzb9cez06eca43d9cda
Decoding Epilepsy Risk: Insights from Genome-Wide Association Studies
Focșa, I. O. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1016108
mTORC2-Nav1.2 signaling drives early hyperexcitability in Alzheimer’s disease mouse model
Dvorak, N. M., & Noebels, J. (2026) · Channels · doi:10.1080/19336950.2026.2687246
Szekeres‐Paraczky, C., Szocsics, P., Erőss, L., Mihály, O. S., & Maglóczky, Z. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146326
Fournier, N. M., Horsey, E., Maletta, T. A., Ekins, G., Brandt, L., Huber, R. J., & Lehmann, H. (2026) · Epilepsy Research · doi:10.1016/j.eplepsyres.2026.107894
- Authors
- Baulac, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Baulac, S.
- ORCID
- Baulac, S.
- Venue
- Progress in Brain Research
- Publisher
- Elsevier
- Published
- 2016
- Volume
- 226
- Pages
- 61-79
- ISSN
- 0079-6123 (ISSN-L)
- OpenAlex
- W2469910147
- Cited by
- 84
- References
- 41
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 12 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 12 · 2017: 5 · 2016: 5
- FWCI
- 45.92
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- focal epilepsy, mTOR signaling, GATOR1 complex, DEPDC5, NPRL2, NPRL3, mTOR, germline mutations, somatic mutations, focal cortical dysplasia, hemimegalencephaly, monogenic epilepsy, mTORC1, epilepsy genetics
- MeSH terms
- Animals, Epilepsies, Partial, Humans, Mutation, Repressor Proteins, Signal Transduction, Genetic Predisposition to Disease, GTPase-Activating Proteins, Tumor Suppressor Proteins, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
