Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy
Open accessAbstract
Objective: Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Recently, we identified mutations in DEPDC5 as a cause of familial focal epilepsy. In this study, we investigated whether mutations in the mammalian target of rapamycin (mTOR) regulators, NPRL2 and NPRL3 , also contribute to cases of focal epilepsy. Methods: We used targeted capture and next‐generation sequencing to analyze 404 unrelated probands with focal epilepsy. We performed exome sequencing on two families with multiple members affected with focal epilepsy and linkage analysis on one of these. Results: In our cohort of 404 unrelated focal epilepsy patients, we identified five mutations in NPRL2 and five in NPRL3 . Exome sequencing analysis of two families with focal epilepsy identified NPRL2 and NPRL3 as the top candidate‐causative genes. Some patients had focal epilepsy associated with brain malformations. We also identified 18 new mutations in DEPDC5 . Interpretation: We have identified NPRL2 and NPRL3 as two new focal epilepsy genes that also play a role in the mTOR‐signaling pathway. Our findings show that mutations in GATOR1 complex genes are the most significant cause of familial focal epilepsy identified to date, including cases with brain malformations. It is possible that deregulation of cellular growth control plays a more important role in epilepsy than is currently recognized. ANN NEUROL 2016;79:120–131
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Cites
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889 · see citing works
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437 · see citing works
A method and server for predicting damaging missense mutations.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., & Sunyaev, S. R. (2010) · Nature Methods · doi:10.1038/nmeth0410-248 · Cited by 13,194 · see citing works
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816 · see citing works
Van der Auwera, G. A., Carneiro, M. O., Hartl, C., Poplin, R., del Angel, G., Levy‐Moonshine, A., Jordan, T., Shakir, K., Roazen, D., Thibault, J., et al. (2013) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1110s43 · Cited by 6,687 · see citing works
Kumar, P., Henikoff, S., & Ng, P. C. (2009) · Nature Protocols · doi:10.1038/nprot.2009.86 · Cited by 6,521 · see citing works
Berg, A. T., Berkovic, S. F., Brodie, M. J., Buchhalter, J., Cross, J. H., Van Emde Boas, W., Engel, J., French, J., Glauser, T. A., Mathern, G. W., et al. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02522.x · Cited by 4,363 · see citing works
Self-citationMerlin—rapid analysis of dense genetic maps using sparse gene flow trees
Abecasis, G. R., Cherny, S. S., Cookson, W., & Cardon, L. R. (2001) · Nature Genetics · doi:10.1038/ng786 · Cited by 3,323 · see citing works
MutationTaster evaluates disease-causing potential of sequence alterations
Schwarz, J. M., Rödelsperger, C., Schuelke, M., & Seelow, D. (2010) · Nature Methods · doi:10.1038/nmeth0810-575 · Cited by 2,975 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911 · see citing works
Identification of the Tuberous Sclerosis Gene <i>TSC1</i> on Chromosome 9q34
Slegtenhorst, M. V., Hoogt, R. D., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., Ouweland, A. V. D., Halley, D., Young, J., et al. (1997) · Science · doi:10.1126/science.277.5327.805 · Cited by 1,648 · see citing works
Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,211 · 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 · cited 2× · see citing works
“This complex has been shown to act as a GAP (GTPase-activating protein) for the RagA/B GTPases, which control mTORC1 (mammalian target of rapamycin complex 1) activity.(5) mammalian target of rapamycin (mTOR) is a master regulator of cell growth, and deregulation of mTOR signaling has been associated with multiple dis…”
BackgroundInsulin Activation of Rheb, a Mediator of mTOR/S6K/4E-BP Signaling, Is Inhibited by TSC1 and 2
Garami, A., Zwartkruis, F. J. T., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S. C., Hafen, E., Bos, J. L., & Thomas, G. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00220-x · Cited by 1,043 · see citing works
Rheb Binds and Regulates the mTOR Kinase
Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., & Avruch, J. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.053 · Cited by 1,005 · see citing works
Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
Petrovski, S., Wang, Q., Heinzen, E. L., Allen, A. S., & Goldstein, D. B. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003709 · Cited by 901 · see citing works
Menon, S., Dibble, C. C., Talbott, G., Hoxhaj, G., Valvezan, A., Takahashi, H., Cantley, L., & Manning, B. (2014) · Cell · doi:10.1016/j.cell.2013.11.049 · Cited by 787 · see citing works
Patches of Disorganization in the Neocortex of Children with Autism
Stoner, R., Chow, M. L., Boyle, M. P., Sunkin, S. M., Mouton, P. R., Roy, S., Wynshaw-Boris, A., Colamarino, S. A., Lein, E. S., & Courchesne, E. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307491 · Cited by 722 · see citing works
De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly
Lee, J. H., Huynh, M., Silhavy, J. L., Kim, S., Dixon-Salazar, T., Heiberg, A., Scott, E., Bafna, V., Hill, K. J., Collazo, A., et al. (2012) · Nature Genetics · doi:10.1038/ng.2329 · Cited by 703 · see citing works
Dazert, E., & Hall, M. N. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.09.003 · Cited by 460 · see citing works
Ngugi, A. K., Kariuki, S. M., Bottomley, C., Kleinschmidt, I., Sander, J. W. A. S., & Newton, C. R. J. C. (2011) · Neurology · doi:10.1212/wnl.0b013e31822cfc90 · Cited by 427 · see citing works
Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., et al. (2012) · Nature Genetics · doi:10.1038/ng.2440 · Cited by 411 · see citing works
Self-citationMutations 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
Self-citationPanchaud, 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
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
EXCAVATOR: detecting copy number variants from whole-exome sequencing data
Magi, A., Tattini, L., Cifola, I., D’Aurizio, R., Benelli, M., Mangano, E., Battaglia, C., Bonora, E., Kurg, A., Seri, M., et al. (2013) · Genome biology · doi:10.1186/gb-2013-14-10-r120 · Cited by 231 · see citing works
Self-citationScheffer, 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
Self-citationLocalization of Rheb to the endomembrane is critical for its signaling function
Buerger, C., DeVries, B., & Stambolic, V. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.03.220 · Cited by 192 · see citing works
Rapamycin suppresses seizures and neuronal hypertrophy in a mouse model of cortical dysplasia
Ljungberg, M. C., Sunnen, C. N., Lugo, J. N., Anderson, A. E., & D’Arcangelo, G. (2009) · Disease Models & Mechanisms · doi:10.1242/dmm.002386 · Cited by 186 · see citing works
Mammalian Target of Rapamycin (mTOR) Pathways in Neurological Diseases
Wong, M. (2013) · Biomedical Journal · doi:10.4103/2319-4170.110365 · Cited by 169 · see citing works
Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia
Ljungberg, M. C., Bhattacharjee, M. B., Lu, Y., Armstrong, D. L., Yoshor, D., Swann, J. W., Sheldon, M., & D’Arcangelo, G. (2006) · Annals of Neurology · doi:10.1002/ana.20949 · Cited by 155 · see citing works
Inactivation of mTORC1 in the Developing Brain Causes Microcephaly and Affects Gliogenesis
Cloëtta, D., Thomanetz, V., Baranek, C., Lustenberger, R. M., Lin, S., Oliveri, F., Atanasoski, S., & Rüegg, M. A. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3294-12.2013 · Cited by 145 · see citing works
Saito, K. (2005) · The Journal of Biochemistry · doi:10.1093/jb/mvi046 · Cited by 128 · see citing works
Validation of a Questionnaire for Clinical Seizure Diagnosis
Reutens, D. C., Howell, R. A., Gebert, K. E., & Berkovic, S. F. (1992) · Epilepsia · doi:10.1111/j.1528-1157.1992.tb01760.x · Cited by 127 · see citing works
Self-citationRapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder
Parker, W. E., Orlova, K. A., Parker, W. H., Birnbaum, J. F., Krymskaya, V. P., Goncharov, D. A., Baybis, M., Helfferich, J., Okochi, K., Strauss, K. A., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005271 · Cited by 121 · see citing works
Role of the mTOR signaling pathway in epilepsy.
Meng, X.-F., Yu, J.-T., Song, J.-H., Chi, S., & Tan, L. (2013) · Journal of Neurological Sciences · doi:10.1016/j.jns.2013.05.029 · Cited by 117 · see citing works
Susceptibility genes for complex epilepsy
Mulley, J. C., Scheffer, I. E., Harkin, L. A., Berkovic, S. F., & Dibbens, L. M. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi355 · Cited by 110 · see citing works
Self-citationBraakman, H. M. H., Vaessen, M. J., Hofman, P. A. M., Hall, M. H. J. A. D.-V., Backes, W. H., Vles, J. S. H., & Aldenkamp, A. P. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03057.x · Cited by 103 · 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
Self-citationSmith, K. R., Bromhead, C. J., Hildebrand, M. S., Shearer, A. E., Lockhart, P. J., Najmabadi, H., Leventer, R. J., McGillivray, G., Amor, D. J., Smith, R. J., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-9-r85 · Cited by 81 · see citing works
When drugs and surgery don’t work
Cascino, G. D. (2008) · Epilepsia · doi:10.1111/j.1528-1167.2008.01930.x · Cited by 60 · see citing works
Brain overgrowth in disorders of RTK–PI3K–AKT signaling: A mosaic of malformations
Hevner, R. F. (2014) · Seminars in Perinatology · doi:10.1053/j.semperi.2014.10.006 · Cited by 59 · see citing works
Steinlein, O. K., Hoda, J., Bertrand, S., & Bertrand, D. (2011) · Seizure · doi:10.1016/j.seizure.2011.10.003 · Cited by 40 · see citing works
Genetics of Temporal Lobe Epilepsy: A Review
Salzmann, A., & Malafosse, A. (2012) · Epilepsy Research and Treatment · doi:10.1155/2012/863702 · Cited by 36 · see citing works
van Kranenburg, M., Hoogeveen-Westerveld, M., & Nellist, M. (2015) · Human Mutation · doi:10.1002/humu.22723 · Cited by 30 · see citing works
PRIMA1 mutation: a new cause of nocturnal frontal lobe epilepsy
Hildebrand, M. S., Tankard, R. M., Gazina, E. V., Damiano, J. A., Lawrence, K. M., Dahl, H. M., Regan, B. M., Shearer, A. E., Smith, R. J., Marini, C., et al. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.224 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555 · see citing works
Thijs, R. D., Surges, R., O'Brien, T. J., & Sander, J. W. A. S. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32596-0 · Cited by 2,203 · see citing works
Devinsky, O., Vezzani, A., O'Brien, T. J., Jetté, N., Scheffer, I. E., de Curtis, M., & Perucca, P. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.24 · Cited by 967 · see citing works
Self-citationSudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention
Devinsky, O., Hesdorffer, D. C., Thurman, D. J., Lhatoo, S. D., & Richerson, G. B. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30158-2 · Cited by 725 · see citing works
The mTOR signalling cascade: paving new roads to cure neurological disease
Crino, P. B. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.81 · Cited by 368 · see citing works
Riney, K., Bogacz, A., Somerville, E., Hirsch, E., Nabbout, R., Scheffer, I. E., Zuberi, S. M., Alsaadi, T., Jain, S., French, J., et al. (2022) · Epilepsia · doi:10.1111/epi.17240 · Cited by 287 · see citing works
Self-citationGoul, C., Peruzzo, R., & Zoncu, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00641-8 · Cited by 269 · see citing works
Translation deregulation in human disease
Tahmasebi, S., Khoutorsky, A., Mathews, M. B., & Sonenberg, N. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0034-x · Cited by 255 · see citing works
The 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
Self-citationReview: 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
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-citationKhan, S., Nobili, L., Khatami, R., Loddenkemper, T., Cajochen, C., Dijk, D., & Eriksson, S. H. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30335-1 · Cited by 168 · see citing works
Germline 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-citationBalestrini, S., & Sisodiya, S. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.01.014 · Cited by 158 · see citing works
Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy
Winawer, M. R., Griffin, N. G., Samanamud, J. L., Baugh, E. H., Rathakrishnan, D., Ramalingam, S., Zagzag, D., Schevon, C. A., Dugan, P. C., Hegde, M., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25243 · Cited by 134 · see citing works
Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort
Rochtus, A. M., Olson, H. E., Smith, L. A., Keith, L. G., Achkar, C. M. E., Taylor, A., Mahida, S., Park, M., Kelly, M., Shain, C., et al. (2020) · Epilepsia · doi:10.1111/epi.16427 · Cited by 132 · 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
Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment
Symonds, J. D., Zuberi, S. M., & Johnson, M. R. (2017) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000433 · Cited by 122 · see citing works
Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy.
Perucca, P., Scheffer, I., Harvey, A., James, P., Lunke, S., Thorne, N., Gaff, C., Regan, B. M., Damiano, J., Hildebrand, M. S., et al. (2017) · Epilepsy Research · doi:10.1016/j.eplepsyres.2017.02.001 · Cited by 103 · see citing works
Self-citationMalformations of Cerebral Cortex Development: Molecules and Mechanisms
Juric‐Sekhar, G., & Hevner, R. F. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012927 · Cited by 116 · see citing works
Yuskaitis, C. J., Jones, B. M., Wolfson, R. L., Super, C. E., Dhamne, S., Rotenberg, A., Sabatini, D., Şahin, M., & Poduri, A. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.12.010 · Cited by 92 · see citing works
Ferguson, S. M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.04.005 · Cited by 101 · 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
Neocortical development and epilepsy: insights from focal cortical dysplasia and brain tumours.
Blümcke, I., Budday, S., Poduri, A., Lal, D., Kobow, K., & Baulac, S. (2021) · Lancet Neurology · doi:10.1016/s1474-4422(21)00265-9 · Cited by 83 · see citing works
Li, M., Yu, J. S. L., Tilgner, K., Ong, S., Koike-Yusa, H., & Yusa, K. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.027 · Cited by 81 · see citing works
Iffland, P. H., Carson, V., Bordey, A., & Crino, P. B. (2019) · Epilepsia · doi:10.1111/epi.16370 · Cited by 84 · see citing works
mTOR signaling pathway genes in focal epilepsies
Baulac, S. (2016) · Progress in Brain Research · doi:10.1016/bs.pbr.2016.04.013 · Cited by 84 · see citing works
Sleep and epilepsy: A snapshot of knowledge and future research lines
Nobili, L., Frauscher, B., Eriksson, S. H., Gibbs, S. A., Halász, P., Lambert, I., Manni, R., Peter‐Derex, L., Proserpio, P., Provini, F., et al. (2022) · Journal of Sleep Research · doi:10.1111/jsr.13622 · Cited by 81 · see citing works
GATOR1 complex: the common genetic actor in focal epilepsies
Baldassari, S., Licchetta, L., Tinuper, P., Bisulli, F., & Pippucci, T. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2016-103883 · Cited by 80 · see citing works
Self-citationSecond‐hit DEPDC5 mutation is limited to dysmorphic neurons in cortical dysplasia type IIA
Lee, W. S., Stephenson, S. E. M., Howell, K. B., Pope, K., Gillies, G., Wray, A. C., Maixner, W. J., Mandelstam, S. A., Berkovic, S. F., Scheffer, I. E., et al. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50815 · Cited by 80 · see citing works
Self-citationPrecision medicine in genetic epilepsies: break of dawn?
Reif, P., Tsai, M.-H., Helbig, I., Rosenow, F., & Klein, K. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1253476 · Cited by 67 · see citing works
microRNAs in the pathophysiology of epilepsy
Brennan, G. P., & Henshall, D. C. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.01.017 · Cited by 73 · see citing works
Opposing functions of β-arrestin 1 and 2 in Parkinson’s disease via microglia inflammation and Nprl3
Fang, Y.-Q., Jiang, Q.-Y., Li, S.-S., Zhu, H., Xu, R., Song, N., Ding, X., Liu, J., Chen, M., Song, M., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00704-9 · Cited by 52 · see citing works
Sleep-related hypermotor epilepsy: prevalence, impact and management strategies
Menghi, V., Bisulli, F., Tinuper, P., & Nobili, L. (2018) · Nature and Science of Sleep · doi:10.2147/nss.s152624 · Cited by 52 · see citing works
Self-citationThe current landscape of epilepsy genetics: where are we, and where are we going?
Ruggiero, S. M., Xian, J., & Helbig, I. (2023) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001141 · Cited by 68 · see citing works
The mTOR Pathway in Treatment of Epilepsy: A clinical update
Griffith, J. L., & Wong, M. L. (2018) · Future Neurology · doi:10.2217/fnl-2018-0001 · Cited by 67 · see citing works
Non-canonical mTOR-Independent Role of DEPDC5 in Regulating GABAergic Network Development.
Swaminathan, A., Hassan-Abdi, R., Renault, S., Siekierska, A., Riché, R., Liao, M.-J., de Witte, P. D., Yanicostas, C., Soussi-Yanicostas, N., Drapeau, P., et al. (2018) · Current Biology · doi:10.1016/j.cub.2018.04.061 · Cited by 49 · see citing works
Hughes, J. N., Dawson, R. E., Tea, M. N., McAninch, D., Piltz, S. G., Jackson, D., Stewart, L. W., Ricos, M. G., Dibbens, L., Harvey, N. L., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-12574-2 · Cited by 53 · see citing works
Self-citationMotelow, J. E., Povysil, G., Dhindsa, R. S., Stanley, K. E., Allen, A. S., Feng, Y. A., Howrigan, D. P., Abbott, L. E., Tashman, K. C., Cerrato, F. E., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.04.009 · Cited by 53 · see citing works
Self-citationDetection of brain somatic variation in epilepsy‐associated developmental lesions
Bedrosian, T. A., Miller, K. E., Grischow, O. E., Schieffer, K. M., LaHaye, S., Yoon, H., Miller, A. R., Navarro, J. B., Westfall, J. J., Leraas, K., et al. (2022) · Epilepsia · doi:10.1111/epi.17323 · Cited by 55 · see citing works
From next-generation sequencing to targeted treatment of non-acquired epilepsies
Møller, R. S., Hammer, T. B., Rubboli, G., Lemke, J. R., & Johannesen, K. M. (2019) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2019.1573144 · Cited by 54 · see citing works
Self-citationDepdc5 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
Sleep-related hypermotor epilepsy (SHE): Contribution of known genes in 103 patients
Licchetta, L., Pippucci, T., Baldassari, S., Minardi, R., Provini, F., Mostacci, B., Plazzi, G., Tinuper, P., Bisulli, F., Bianchi, A., et al. (2019) · Seizure · doi:10.1016/j.seizure.2019.11.009 · Cited by 52 · see citing works
Self-citationNicotinic acetylcholine receptors and epilepsy
Becchetti, A., Grandi, L. C., Cerina, M., & Amadeo, A. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106698 · Cited by 53 · see citing works
Koeleman, B. P. C. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.03.042 · Cited by 52 · see citing works
Dawson, 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
Self-citationMan, A., Scipio, M. D., Grewal, S., Suk, Y., Trinari, E., Ejaz, R., & Whitney, R. (2024) · Genes · doi:10.3390/genes15030332 · Cited by 50 · 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
Self-citationLee, W. S., Baldassari, S., Stephenson, S. E. M., Lockhart, P. J., Baulac, S., & Leventer, R. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031344 · Cited by 45 · see citing works
Self-citationPharmacogenetics 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
Genetic characterization identifies bottom-of-sulcus dysplasia as an mTORopathy
Lee, W., Stephenson, S. E. M., Pope, K., Gillies, G., Maixner, W., Macdonald-Laurs, E., MacGregor, D., D'Arcy, C., Jackson, G., Harvey, A., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000010670 · Cited by 31 · 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
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
Bonazzi, S., Goold, C. P., Gray, A. J., Thomsen, N. M., Nunez, J., Karki, R. G., Gorde, A., Biag, J. D., Malik, H. A., Sun, Y., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01398 · Cited by 38 · 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
Richard, A., Scheffer, I. E., & Wilson, S. J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.036 · Cited by 36 · see citing works
Self-citationCardiac Investigations in Sudden Unexpected Death in DEPDC5 ‐Related Epilepsy
Bacq, A., Roussel, D., Bonduelle, T., Zagaglia, S., Maletić, M. M., Ribierre, T., Adle-Biassette, H., Marchal, C., Jennesson, M., An, I., et al. (2021) · Annals of Neurology · doi:10.1002/ana.26256 · Cited by 27 · see citing works
The clinical, imaging, pathological and genetic landscape of bottom-of-sulcus dysplasia
Macdonald‐Laurs, E., Warren, A. E. L., Francis, P. S. J., Mandelstam, S. A., Lee, W. S., Coleman, M., Stephenson, S. E. M., Barton, S., D’Arcy, C. E., Lockhart, P. J., et al. (2023) · Brain · doi:10.1093/brain/awad379 · Cited by 31 · 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
Krenn, M., Wagner, M., Hotzy, C., Graf, E., Weber, S., Brunet, T., Lorenz‐Depiereux, B., Kasprian, G. J., Aull‐Watschinger, S., Pataraia, E., et al. (2020) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2019-106658 · Cited by 33 · see citing works
Clinical Letter: A case report of targeted therapy with sirolimus for NPRL3 epilepsy.
Vawter-Lee, M., Franz, D., Fuller, C., & Greiner, H. (2019) · Seizure · doi:10.1016/j.seizure.2019.10.007 · Cited by 29 · see citing works
Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology
Becchetti, A., Grandi, L. C., Colombo, G., Meneghini, S., & Amadeo, A. (2020) · Brain Sciences · doi:10.3390/brainsci10120907 · Cited by 31 · see citing works
Rácz, Á., Becker, A. J., Quesada, C. M., Borger, V., Vatter, H., Surges, R., & Elger, C. E. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.666056 · Cited by 28 · see citing works
Familial mesial temporal lobe epilepsy and the borderland of déjà vu
Perucca, P., Crompton, D. E., Bellows, S. T., McIntosh, A. M., Kalinčík, T., Newton, M. R., Vajda, F. J. E., Scheffer, I. E., Kwan, P., O'Brien, T. J., et al. (2017) · Annals of Neurology · doi:10.1002/ana.24984 · Cited by 27 · see citing works
Self-citationBeňová, B., & Jacques, T. S. (2018) · Brain Pathology · doi:10.1111/bpa.12686 · Cited by 26 · see citing works
Jiang, T., Gao, J., Jiang, L., Lu, C., Zhao, C., Su, X., Shen, Y., Gu, W., Kong, X., Yang, Y., et al. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.699574 · Cited by 26 · see citing works
Sleep Related Epilepsy and Pharmacotherapy: An Insight
Kumar, J., Solaiman, A., Mahakkanukrauh, P., Mohamed, R., & Das, S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01088 · Cited by 23 · see citing works
Beňová, B., Sanders, M. W. C. B., Mészárosová, A. U., Bělohlávková, A., Splítková, B., Novák, V., Staněk, D., Vlčková, M., Zámečnı́k, J., Aronica, E., et al. (2021) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2020.12.001 · Cited by 25 · see citing works
Myers, K. (2022) · Continuum · doi:10.1212/con.0000000000001077 · Cited by 23 · see citing works
Contribution of ultrarare variants in mTOR pathway genes to sporadic focal epilepsies
Pippucci, T., Licchetta, L., Baldassari, S., Marconi, C., Luise, M. D., Myers, C. T., Nardi, E., Provini, F., Cameli, C., Minardi, R., et al. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.722 · Cited by 25 · see citing works
Self-citationViswanathan, S., Oliver, K. L., Regan, B. M., Schneider, A. L., Myers, C. T., Mehaffey, M. G., LaCroix, A. J., Antony, J., Webster, R., Cardamone, M., et al. (2024) · Annals of Neurology · doi:10.1002/ana.27041 · Cited by 23 · see citing works
Self-citationEvidence for a Dual-Pathway, 2-Hit Genetic Model for Focal Cortical Dysplasia and Epilepsy
Bennett, M., Hildebrand, M., Kayumi, S., Corbett, M., Gupta, S., Ye, Z.-M., Krivanek, M., Burgess, R., Henry, O. J., Damiano, J., et al. (2022) · Neurology: Genetics · doi:10.1212/nxg.0000000000000652 · Cited by 19 · see citing works
Self-citationDefective lipid signalling caused by mutations inPIK3C2Bunderlies focal epilepsy
Gozzelino, L., Kochlamazashvili, G., Baldassari, S., Mackintosh, A. I., Licchetta, L., Iovino, E., Liu, Y. C., Bennett, C. A., Bennett, M. F., Damiano, J. A., et al. (2022) · Brain · doi:10.1093/brain/awac082 · Cited by 23 · see citing works
Self-citationHarris, R. V., Oliver, K. L., Perucca, P., Striano, P., Labate, A., Riva, A., Grinton, B. E., Reid, J., Hutton, J., Todaro, M., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26765 · Cited by 23 · see citing works
Self-citationCanavati, C., Klein, K., Afawi, Z., Pendziwiat, M., Rayyan, A. A., Kamal, L., Zahdeh, F., Qaysia, I., Helbig, I., & Kanaan, M. (2019) · Epilepsia · doi:10.1111/epi.15665 · Cited by 20 · see citing works
Dorsal telencephalon-specific Nprl2- and Nprl3-knockout mice: novel mouse models for GATORopathy
Ishida, S., Zhao, D., Sawada, Y., Hiraoka, Y., Mashimo, T., & Tanaka, K. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab337 · Cited by 22 · see citing works
Wang, H., Liu, W., Zhang, Y.-H., Liu, Q.-Z., Cai, L.-X., & Jiang, Y.-W. (2023) · Epilepsia Open · doi:10.1002/epi4.12770 · Cited by 23 · see citing works
Klein, K. M., Pendziwiat, M., Eilam, A., Gilad, R., Blatt, I., Rosenow, F., Kanaan, M. N., Helbig, I., & Afawi, Z. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8539-3 · Cited by 21 · see citing works
Auvin, S., & Baulac, S. (2023) · Revue Neurologique · doi:10.1016/j.neurol.2022.12.007 · Cited by 20 · see citing works
Genetic investigations of the epileptic encephalopathies
Myers, C. T., & Mefford, H. C. (2016) · Progress in brain research · doi:10.1016/bs.pbr.2016.04.006 · Cited by 20 · see citing works
Chandrasekar, I., Tourney, A., Loo, K., Carmichael, J., James, K. N., Ellsworth, K. A., Dimmock, D., & Joseph, M. (2021) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62185 · Cited by 18 · see citing works
Zhang, X., Huang, Z., Liu, J., Li, M., Zhao, X., Ye, J., & Wang, Y. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.641019 · Cited by 18 · see citing works
Sleep-Related Hypermotor Epilepsy: Etiology, Electro-Clinical Features, and Therapeutic Strategies
Wan, H., Wang, X., Chen, Y., Jiang, B., Chen, Y., Hu, W., Zhang, K., & Shao, X. (2021) · Nature and Science of Sleep · doi:10.2147/nss.s330986 · Cited by 18 · see citing works
C.4 Neurologic injury in pediatric patients cannulated for rescue extracorporeal life support
Buttle, S., Woodward, K., Foster, L., Yee, P., Kirton, A., Jamal, S., Mineyko, A., Blackwood, J., & Esser, M. (2024) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1007/s00415-023-12174-3 · Cited by 14 · see citing works
A stereo EEG study in a patient with sleep-related hypermotor epilepsy due to DEPDC5 mutation
Ferri, L., Bisulli, F., Mai, R., Licchetta, L., Leta, C., Nobili, L., Mostacci, B., Pippucci, T., & Tinuper, P. (2017) · Seizure · doi:10.1016/j.seizure.2017.10.022 · Cited by 17 · see citing works
Self-citationGenetics of Epileptic Networks: from Focal to Generalized Genetic Epilepsies
Qaiser, F., Yuen, R. K. C., & Andrade, D. M. (2020) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-020-01059-x · Cited by 17 · see citing works
García-Rincón, D., Díaz-Alonso, J., Paraíso‐Luna, J., Ortega, Z., Aguareles, J., de Salas-Quiroga, A., Jou, C., de Prada, I., Martínez‐Cerdeño, V., Aronica, E., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01508 · Cited by 16 · see citing works
Loissell-Baltazar, Y. A., & Dokudovskaya, S. (2021) · Cells · doi:10.3390/cells10102689 · Cited by 17 · see citing works
The interaction between circadian rhythm and epilepsy
Liu, M., Ding, J., & Wang, X. (2022) · Acta Epileptologica · doi:10.1186/s42494-022-00094-0 · Cited by 15 · see citing works
He, N., Guan, B., Wang, J., Liu, H., Mao, Y., Liu, Z., Yin, F., Peng, J., Xiao, B., Tang, B., et al. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1289 · Cited by 15 · see citing works
The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development
Ma, Q., Chen, G., Li, Y., Guo, Z., & Zhang, X. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.04.041 · Cited by 15 · see citing works
Wan, L., Shi, X.-Y., Ge, W., Sun, Y.-L., Zhang, S., Wang, J., Hu, L., Zou, L., & Yang, G. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.497225 · 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
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
Clinical phenotypic and genotypic characterization of NPRL3-related epilepsy
Zhang, H., Deng, J., Wang, X., Chen, C., Chen, S., Dai, L., & Fang, F. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1113747 · Cited by 12 · see citing works
Dainelli, A., Iacomino, M., Rossato, S., Bugin, S., Traverso, M., Severino, M., Gustincich, S., Capra, V., Duca, M. D., Zara, F., et al. (2023) · Epilepsia Open · doi:10.1002/epi4.12798 · Cited by 11 · see citing works
Ryu, C., Bae, J., Kim, I., Kim, J., Oh, S.-H., Kim, O., & Kim, N. (2020) · Diagnostics · doi:10.3390/diagnostics10110947 · Cited by 11 · see citing works
- Authors
- 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., Baldassari, S., Palombo, F., Epilepsy Electroclinical Study Group, Santucci, M., Meletti, S., Berkovic, S. F., Rubboli, G., Thomas, P. Q., Scheffer, I. E., Tinuper, P., Geoghegan, J., Schreiber, A. W., & Dibbens, L. M.
- Affiliations
- University of South Australia (AU)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Novocraft Technologies Sdn Bhd Selangor Malaysia
- Istituto delle Scienze Neurologiche di Bologna (IT)
- The University of Adelaide (AU)
- University of Modena and Reggio Emilia (IT)
- The University of Melbourne (AU)
- University of Copenhagen (DK)
- Royal Children's Hospital (AU)
- South Australia Pathology (AU)
- Corresponding author
- Dibbens, Leanne M.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2015-12-12
- Volume
- 79
- Issue
- 1
- Pages
- 120-131
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2302804942
- Cited by
- 246
- References
- 50
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 21 · 2023: 25 · 2022: 24 · 2021: 23 · 2020: 41 · 2019: 19 · 2018: 23 · 2017: 20 · 2016: 13
- FWCI
- 15.14
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- Australian Cancer Research Foundation
- National Health and Medical Research Council
- National Medical Research Council
- 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, NPRL2, NPRL3, mTOR signaling, GATOR1 complex, genetic epilepsy, brain malformations, familial epilepsy
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Epilepsies, Partial, Humans, Mutation, Pedigree, Repressor Proteins, Signal Transduction, Sequence Analysis, DNA, GTPase-Activating Proteins, Gene Expression Profiling, Tumor Suppressor Proteins, Multiprotein Complexes, TOR Serine-Threonine Kinases, Exome
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