A Nonsense Mutation of the Sodium Channel Gene SCN2A in a Patient with Intractable Epilepsy and Mental Decline
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Mutations, exclusively missense, of voltage-gated sodium channel α subunit type 1 (SCN1A) and type 2 (SCN2A) genes were reported in patients with idiopathic epilepsy: generalized epilepsy with febrile seizures plus. Nonsense and frameshift mutations of SCN1A, by contrast, were identified in intractable epilepsy: severe myoclonic epilepsy in infancy (SMEI). Here we describe a first nonsense mutation of SCN2A in a patient with intractable epilepsy and severe mental decline. The phenotype is similar to SMEI but distinct because of partial epilepsy, delayed onset (1 year 7 months), and absence of temperature sensitivity. A mutational analysis revealed that the patient had a heterozygous de novo nonsense mutation R102X of SCN2A. Patch-clamp analysis of Na v 1.2 wild-type channels and the R102X mutant protein coexpressed in human embryonic kidney 293 cells showed that the truncated mutant protein shifted the voltage dependence of inactivation of wild-type channels in the hyperpolarizing direction. Analysis of the subcellular localization of R102X truncated protein suggested that its dominant negative effect could arise from direct or indirect cytoskeletal interactions of the mutant protein. Haploinsufficiency of Na v 1.2 protein is one plausible explanation for the pathology of this patient; however, our biophysical findings suggest that the R102X truncated protein exerts a dominant negative effect leading to the patient's intractable epilepsy.
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SCN2A is the second strongest overall association, with two truncating mutations in ASD cases and three in ID cases.
“The second strongest overall association, with two truncating mutations in ASD cases and three such mutations in ID cases, is SCN2A, a gene previously associated with epilepsy and seizure disorders [52,53].”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [52]
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Cites
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
Ionic channels of excitable membranes
(1985) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(85)90172-7 · Cited by 7,133 · see citing works
De Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of Infancy
Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., & De Jonghe, P. (2001) · The American Journal of Human Genetics · doi:10.1086/320609 · Cited by 1,292 · see citing works
Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2
Escayg, A., MacDonald, B. T., Meisler, M. H., Baulac, S., Huberfeld, G., An-Gourfinkel, I., Brice, A., LeGuern, E., Moulard, B., Chaigne, D., et al. (2000) · Nature Genetics · doi:10.1038/74159 · Cited by 996 · see citing works
Wallace, R. H., Wang, D. W., Singh, R., Scheffer, I. E., George, A. L., Phillips, H. A., Saar, K., Reis, A., Johnson, E. W., Sutherland, G. R., et al. (1998) · Nature Genetics · doi:10.1038/1252 · Cited by 996 · see citing works
(2005) · Cited by 944 · see citing works
Hentze, M. W., & Kulozik, A. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80542-5 · Cited by 809 · see citing works
Mutant GABAA receptor γ2-subunit in childhood absence epilepsy and febrile seizures
Wallace, R. H., Marini, C., Petrou, S., Harkin, L. A., Bowser, D. N., Panchal, R. G., Williams, D. A., Sutherland, G. R., Mulley, J. C., Scheffer, I. E., et al. (2001) · Nature Genetics · doi:10.1038/ng0501-49 · Cited by 780 · see citing works
First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the γ2-subunit gene
Baulac, S., Huberfeld, G., Gourfinkel‐An, I., Mitropoulou, G., Beranger, A., Prud’homme, J.-F., Baulac, M., Brice, A., Bruzzone, R., & Leguern, É. (2001) · Nature Genetics · doi:10.1038/ng0501-46 · Cited by 765 · see citing works
Scheffer, I. E. (1997) · Brain · doi:10.1093/brain/120.3.479 · Cited by 758 · see citing works
Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel
Isom, L. L., Jongh, K. S. D., Patton, D., Reber, B. F. X., Offord, J., Charbonneau, H., Walsh, K. A., Goldin, A. L., & Catterall, W. A. (1992) · Science · doi:10.1126/science.1375395 · Cited by 711 · see citing works
Harkin, L. A., Bowser, D. N., Dibbens, L. M., Singh, R., Phillips, F., Wallace, R. H., Richards, M. C., Williams, D. A., Mulley, J. C., Berkovic, S. F., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/338710 · Cited by 441 · see citing works
Sodium Channel β4, a New Disulfide-Linked Auxiliary Subunit with Similarity to β2
Yu, F. H., Westenbroek, R. E., Silos‐Santiago, I., McCormick, K. A., Lawson, D., Ge, P., Ferriera, H., Lilly, J., DiStefano, P. S., Catterall, W. A., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07577.2003 · Cited by 393 · see citing works
Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel
Jouvenceau, A., Eunson, L. H., Spauschus, A., Ramesh, V., Zuberi, S. M., Kullmann, D. M., & Hanna, M. G. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05971-2 · Cited by 386 · see citing works
Sodium-channel defects in benign familial neonatal-infantile seizures
Heron, S. E., Crossland, K. M., Andermann, E., Phillips, H. A., Hall, A. J., Bleasel, A., Shevell, M. I., Mercho, S., Seni, M., Guiot, M., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09968-3 · Cited by 378 · see citing works
Sugawara, T., Tsurubuchi, Y., Agarwala, K. L., Ito, M., Fukuma, G., Mazaki-Miyazaki, E., Nagafuji, H., Noda, M., Imoto, K., Wada, K., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111065098 · Cited by 378 · see citing works
Self-citationMolecular Basis of an Inherited Epilepsy
Lossin, C., Wang, D. W., Rhodes, T. H., Vanoye, C. G., & George, A. L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00714-6 · Cited by 361 · see citing works
Fujiwara, T. (2003) · Brain · doi:10.1093/brain/awg053 · Cited by 345 · see citing works
Self-citationNeuronal Sodium-Channel α1-Subunit Mutations in Generalized Epilepsy with Febrile Seizures Plus
Wallace, R. H., Scheffer, I. E., Barnett, S., Richards, M. C., Dibbens, L. M., Desai, R. R., Lerman‐Sagie, T., Lev, D., Mazarib, A., Brand, N. R., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/319516 · Cited by 343 · see citing works
Functional specialization of the axon initial segment by isoform-specific sodium channel targeting
Boiko, T., Van Wart, A., Caldwell, J. H., Levinson, S. R., Trimmer, J. S., & Matthews, G. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-06-02306.2003 · Cited by 311 · see citing works
Morgan, K., Stevens, E. B., Shah, B. S., Cox, P. J., Dixon, A. K., Lee, K., Pinnock, R. D., Hughes, J. M., Richardson, P. J., Mizuguchi, K., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.030362197 · Cited by 299 · see citing works
beta 0 thalassemia, a nonsense mutation in man.
Chang, J. C., & Kan, Y. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.6.2886 · Cited by 294 · see citing works
Escayg, A., Heils, A., MacDonald, B. T., Haug, K., Sander, T., & Meisler, M. H. (2001) · The American Journal of Human Genetics · doi:10.1086/319524 · Cited by 276 · see citing works
Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy
Sugawara, T., Mazaki-Miyazaki, E., Fukushima, K., 下村, 次., Fujiwara, T., Hamano, S., Inoue, Y., & Yamakawa, K. (2002) · Neurology · doi:10.1212/wnl.58.7.1122 · Cited by 236 · see citing works
Self-citationSignificant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy
Ohmori, I., Ouchida, M., Ohtsuka, Y., Oka, E., & Shimizu, K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00617-4 · Cited by 228 · see citing works
Epilepsy-Associated Dysfunction in the Voltage-Gated Neuronal Sodium Channel SCN1A
Lossin, C., Rhodes, T. H., Desai, R. R., Vanoye, C. G., Dao, W., Carniciu, S., Devinsky, O., & George, A. L. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-36-11289.2003 · Cited by 215 · see citing works
Baulac, S., Gourfinkel‐An, I., Picard, F., Rosenberg‐Bourgin, M., Prud’homme, J.-F., Baulac, M., Brice, A., & Leguern, É. (1999) · The American Journal of Human Genetics · doi:10.1086/302593 · Cited by 208 · see citing works
Primary Structure and Functional Expression of the β 1 Subunit of the Rat Brain Sodium Channel
Isom, L. L., Jongh, K. S. D., Patton, D. E., Reber, B. F. X., Offord, J., Charbonneau, H., Walsh, K. A., Goldin, A. L., & Catterall, W. A. (1992) · Science · doi:10.1126/science.256.5058.839 · Cited by 201 · see citing works
Spampanato, J. G., Escayg, A., Meisler, M. H., & Goldin, A. L. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07481.2001 · Cited by 191 · see citing works
Severe myoclonic epilepsy in infants
Dravet, C. (1992) · Medical Entomology and Zoology · Cited by 178 · see citing works
Neuronal Death and Perinatal Lethality in Voltage-Gated Sodium Channel αII-Deficient Mice
Planells‐Cases, R., Caprini, M., Zhang, J., Rockenstein, E. M., Rivera, R. R., Murre, C., Masliah, E., & Montal, M. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76829-9 · Cited by 168 · see citing works
Self-citationNa v 1.1 mutations cause febrile seizures associated with afebrile partial seizures
Sugawara, T., Mazaki-Miyazaki, E., Ito, M., Nagafuji, H., Fukuma, G., Mitsudome, A., Wada, K., Kaneko, S., Hirose, S., & Yamakawa, K. (2001) · Neurology · doi:10.1212/wnl.57.4.703 · Cited by 149 · see citing works
Self-citationAkai, J., Makita, N., Sakurada, H., Shirai, N., Ueda, K., Kitabatake, A., Nakazawa, K., Kimura, A., & Hiraoka, M. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01875-5 · Cited by 144 · see citing works
Self-citationMoulard, B., Chaigne, D., Mouthon, D., Burési, C., Guipponi, M., & Malafosse, A. (1999) · The American Journal of Human Genetics · doi:10.1086/302621 · Cited by 135 · see citing works
Cytoskeleton modulates gating of voltage-dependent sodium channel in heart
Undrovinas, A. I., SHANDER, G. S., & Makielski, J. C. (1995) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1995.269.1.h203 · Cited by 124 · see citing works
Jenkins, S. M., & Bennett, V. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042601799 · Cited by 121 · see citing works
Matsumoto, G., & Sakai, H. (1979) · The Journal of Membrane Biology · doi:10.1007/bf01868784 · Cited by 96 · see citing works
Ahmed, C. M. I., Ware, D., Lee, S. C., Patten, C. D., Ferrer-Montiel, A. V., Schinder, A. F., McPherson, J. D., Wagner-McPherson, C., Wasmuth, J. J., & Evans, G. A. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.17.8220 · Cited by 84 · see citing works
First genetic evidence of GABAA receptor dysfunction in epilepsy: A mutation in the γ2-subunit gene
Baulac, S., Huberfeld, G., Gourfinkel‐An, I., Mitropoulou, G., Beranger, A., Prud'homme, J.-F., Baulac, M., Brice, A., Bruzzone, R., & Leguern, É. (2001) · Nature Genetics · doi:10.1038/88254 · Cited by 81 · see citing works
Nav1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents
Sugawara, T., Tsurubuchi, Y., Fujiwara, T., Mazaki-Miyazaki, E., Nagata, K., Montal, M., Inoue, Y., & Yamakawa, K. (2003) · Epilepsy Research · doi:10.1016/s0920-1211(03)00084-6 · Cited by 79 · see citing works
Self-citationMutant GABAAreceptor I32-subunit in childhood absence epilepsy and febrile seizures
Wallace, R. H., Marini, C., Petrou, S., Harkin, L. A., Bowser, D. N., Panchal, R. G., Williams, D. A., Sutherland, G. R., Mulley, J. C., Scheffer, I. E., et al. (2001) · Nature Genetics · doi:10.1038/88259 · Cited by 77 · see citing works
Ito, M., Nagafuji, H., Okazawa, H., Yamakawa, K., Sugawara, T., Mazaki-Miyazaki, E., Hirose, S., Fukuma, G., Mitsudome, A., Wada, K., et al. (2002) · Epilepsy Research · doi:10.1016/s0920-1211(01)00313-8 · Cited by 73 · see citing works
Self-citationAlekov, A. K., Rahman, M. M., Mitrović, N., Lehmann‐Horn, F., & Lerche, H. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01590.x · Cited by 68 · see citing works
Breakdown of cytoskeletal filaments selectively reduces Na and Ca spikes in cultured mammal neurones
Fukuda, J., Kameyama, M., & Yamaguchi, K. (1981) · Nature · doi:10.1038/294082a0 · Cited by 65 · see citing works
Cytoskeleton modulates coupling between availability and activation of cardiac sodium channel
Maltsev, V. A., & Undrovinas, A. I. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.273.4.h1832 · Cited by 57 · see citing works
Myoclonic epilepsies in childhood.
Dravet, C., Roger, J., Bureau, M., & Bernardina, B. D. (1971) · Cited by 57 · see citing works
Interaction of the Nav1.2a Subunit of the Voltage-dependent Sodium Channel with Nodal AnkyrinG
Bouzidi, M., Tricaud, N., Giraud, P., Kordeli, E., Caillol, G., Deleuze, C., Couraud, F., & Alcaraz, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201760200 · Cited by 56 · see citing works
Matsumoto, G., & Sakai, H. (1979) · The Journal of Membrane Biology · doi:10.1007/bf01868785 · Cited by 55 · see citing works
Broca's region revisited: Cytoarchitecture and intersubject variability
Amunts, K., Schleicher, A., B�rgel, U., Mohlberg, H., Uylings, H. B. M., & Zilles, K. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990920)412:2
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De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084 · see citing works
De novo mutations in epileptic encephalopathies
Epi4K Consortium, & Epilepsy Phenome/Genome Project (2013) · Nature · doi:10.1038/nature12439 · Cited by 1,514 · see citing works
Molecular Physiology of Cardiac Repolarization
Nerbonne, J. M., & Kass, R. S. (2005) · Physiological Reviews · doi:10.1152/physrev.00002.2005 · Cited by 1,054 · see citing works
Rauch, A., Wieczorek, D., Graf, E., Wieland, T., Endele, S., Schwarzmayr, T., Albrecht, B., Bartholdi, D., Beygo, J., Di Donato, N., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61480-9 · Cited by 1,041 · see citing works
Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5270-06.2007 · Cited by 879 · see citing works
Self-citationTargeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., et al. (2013) · Nature Genetics · doi:10.1038/ng.2646 · Cited by 687 · see citing works
Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2
Strauss, K. A., Puffenberger, E. G., Huentelman, M. J., Gottlieb, S., Dobrin, S. E., Parod, J. M., Stephan, D. A., & Morton, D. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052773 · Cited by 630 · see citing works
Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders
Wolff, M., Johannesen, K. M., Hedrich, U. B. S., Masnada, S., Rubboli, G., Gardella, E., Lesca, G., Ville, D., Milh, M., Villard, L., et al. (2017) · Brain · doi:10.1093/brain/awx054 · Cited by 600 · see citing works
Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction
Goldberg, E. M., & Coulter, D. A. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3482 · Cited by 542 · see citing works
Sodium channel mutations in epilepsy and other neurological disorders
Meisler, M. H. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25466 · Cited by 512 · see citing works
Clinical application of exome sequencing in undiagnosed genetic conditions
Need, A. C., Shashi, V., Hitomi, Y., Schoch, K., Shianna, K. V., McDonald, M., Meisler, M. H., & Goldstein, D. B. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-100819 · Cited by 438 · see citing works
A de novo convergence of autism genetics and molecular neuroscience
Krumm, N., O’Roak, B. J., Shendure, J., & Eichler, E. E. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2013.11.005 · Cited by 423 · see citing works
Sodium channel SCN1A and epilepsy: Mutations and mechanisms
Escayg, A., & Goldin, A. L. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02640.x · Cited by 398 · see citing works
<i>SCN1A</i>mutations and epilepsy
Mulley, J. C., Scheffer, I. E., Petrou, S., Dibbens, L. M., Berkovic, S. F., & Harkin, L. A. (2005) · Human Mutation · doi:10.1002/humu.20178 · Cited by 351 · see citing works
Berkovic, S. F., Harkin, L. A., McMahon, J. M., Pelekanos, J. T., Zuberi, S. M., Wirrell, E. C., Gill, D. S., Iona, X., Mulley, J. C., & Scheffer, I. E. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70446-x · Cited by 295 · see citing works
Ben-Shalom, R., Keeshen, C. M., Berrios, K. N., An, J. Y., Sanders, S. J., & Bender, K. J. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.01.009 · Cited by 288 · see citing works
Navigating the channels and beyond: unravelling the genetics of the epilepsies
Helbig, I., Scheffer, I. E., Mulley, J. C., & Berkovic, S. F. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70039-5 · Cited by 281 · see citing works
<i>SCN2A</i> encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures
Howell, K. B., McMahon, J. M., Carvill, G. L., Tambunan, D., Mackay, M. T., Rodriguez-Casero, V., Webster, R., Clark, D., Freeman, J. L., Calvert, S., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001926 · Cited by 255 · see citing works
Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology
Catarino, C. B., Liu, J. Y. W., Liagkouras, I., Gibbons, V. S., Labrum, R. W., Ellis, R., Woodward, C., Davis, M. B., Smith, S. J., Cross, J. H., et al. (2011) · Brain · doi:10.1093/brain/awr129 · Cited by 227 · see citing works
Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects
Meisler, M. H., O’Brien, J. E., & Sharkey, L. M. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.188482 · Cited by 215 · see citing works
Mechanisms of human inherited epilepsies
Reid, C. A., Berkovic, S. F., & Petrou, S. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.09.016 · Cited by 207 · see citing works
Ogiwara, I., Ito, K., Sawaishi, Y., Osaka, H., Mazaki, E., Inoue, I., Montal, M., Hashikawa, T., Shike, T., Fujiwara, T., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b9cebc · Cited by 205 · see citing works
Self-citationClinical spectrum of <i>SCN2A</i> mutations expanding to Ohtahara syndrome
Nakamura, K., Kato, M., Osaka, H., Yamashita, S., Nakagawa, E., Haginoya, K., Tohyama, J., Okuda, M., Wada, T., Shimakawa, S., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a43e57 · Cited by 201 · see citing works
Sodium channelopathies in neurodevelopmental disorders
Meisler, M. H., Hill, S. F., & Yu, W. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-00418-4 · Cited by 202 · see citing works
Sodium Channels, Inherited Epilepsy, and Antiepileptic Drugs
Catterall, W. A. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140232 · Cited by 194 · see citing works
Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy
Liao, Y., Deprez, L., Maljevic, S., Pitsch, J., Claes, L., Hristova, D., Jordanova, A., Ala-Mello, S., Bellan-Koch, A., Blazevic, D., et al. (2010) · Brain · doi:10.1093/brain/awq057 · Cited by 185 · see citing works
SCN1A duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis
Marini, C., Scheffer, I. E., Nabbout, R., Mei, D., Cox, K., Dibbens, L. M., McMahon, J. M., Iona, X., Sánchez-Carpintero, R., Elia, M., et al. (2009) · Epilepsia · doi:10.1111/j.1528-1167.2009.02013.x · Cited by 173 · see citing works
Wei, F., Yan, L.-M., Su, T., He, N., Lin, Z.-J., Wang, J., Shi, Y., Yi, Y., & Liao, W. (2017) · Neuroscience Bulletin · doi:10.1007/s12264-017-0134-1 · Cited by 147 · see citing works
Deneault, E., White, S. H., Rodrigues, D. C., Ross, P. J., Faheem, M., Zaslavsky, K., Wang, Z., Alexandrova, R., Pellecchia, G., Wei, W., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.10.003 · Cited by 145 · see citing works
Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review
Menezes, L. F. S., Júnior, E. F. S., Tibery, D. V., Carneiro, L. D. A., & Schwartz, E. F. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01276 · Cited by 137 · see citing works
Sodium channelopathies of skeletal muscle and brain
Mantegazza, M., Cestèle, S., & Catterall, W. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00025.2020 · Cited by 133 · see citing works
Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome
Shi, X., Yasumoto, S., Nakagawa, E., Fukasawa, T., Uchiya, S., & Hirose, S. (2009) · Brain and Development · doi:10.1016/j.braindev.2009.08.009 · Cited by 131 · see citing works
Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotype
Mastrangelo, M., & Leuzzi, V. (2011) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2011.11.003 · Cited by 129 · see citing works
Kullmann, D. M. (2010) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153122 · Cited by 128 · see citing works
The phenotypic spectrum of SCN2A-related epilepsy
Reynolds, C., King, M. D., & Gorman, K. M. (2019) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2019.12.016 · Cited by 126 · see citing works
Scheffer, I. E., French, J. A., Hirsch, É., Jain, S., Mathern, G. W., Moshé, S. L., Perucca, E., Tomson, T., Wiebe, S., Zhang, Y., et al. (2016) · Epilepsia Open · doi:10.1002/epi4.5 · Cited by 125 · see citing works
Clinical spectrum of SCN2A mutations
Shi, X., Yasumoto, S., Kurahashi, H., Nakagawa, E., Fukasawa, T., Uchiya, S., & Hirose, S. (2011) · Brain and Development · doi:10.1016/j.braindev.2011.09.016 · Cited by 122 · see citing works
Impaired cortico-striatal excitatory transmission triggers epilepsy
Miyamoto, H., Tatsukawa, T., Shimohata, A., Yamagata, T., Suzuki, T., Amano, K., Mazaki, E., Raveau, M., Ogiwara, I., Asaka-Oba, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09954-9 · Cited by 121 · see citing works
Self-citationScalmani, P., Rusconi, R., Armatura, E., Zara, F., AVANZINI, G., Franceschetti, S., & Mantegazza, M. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2476-06.2006 · Cited by 120 · see citing works
Action Potential Initiation in Neocortical Inhibitory Interneurons
Li, T., Tian, C., Scalmani, P., Frassoni, C., Mantegazza, M., Wang, Y., Yang, M., Wu, S., & Shu, Y. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001944 · Cited by 115 · see citing works
Nav1.2 haplodeficiency in excitatory neurons causes absence-like seizures in mice
Ogiwara, I., Miyamoto, H., Tatsukawa, T., Yamagata, T., Nakayama, T., Atapour, N., Miura, E., Mazaki, E., Ernst, S. J., Cao, D., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0099-2 · Cited by 111 · see citing works
Self-citationGenetic and epigenetic mechanisms of epilepsy: a review
Chen, T., Giri, M., Xia, Z., Subedi, Y. N., & Li, Y. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s142032 · Cited by 105 · see citing works
Wolff, M., Brunklaus, A., & Zuberi, S. M. (2019) · Epilepsia · doi:10.1111/epi.14935 · Cited by 105 · see citing works
Misra, S. N., Kahlig, K. M., & George, A. L. (2008) · Epilepsia · doi:10.1111/j.1528-1167.2008.01619.x · Cited by 102 · see citing works
Meents, J., Bressan, E., Sontag, S., Foerster, A., Hautvast, P. A. I., Rösseler, C., Hampl, M., Schüler, H. M., Goetzke, R., Le, T. K. C., et al. (2019) · Pain · doi:10.1097/j.pain.0000000000001511 · Cited by 99 · see citing works
Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia
Schwarz, N., Hahn, A., Bast, T., Müller, S., Löffler, H., Maljevic, S., Gaily, E., Prehl, I., Biskup, S., Joensuu, T., et al. (2016) · Journal of Neurology · doi:10.1007/s00415-015-7984-0 · Cited by 95 · see citing works
Novel SCN1A Mutation in a Proband With Malignant Migrating Partial Seizures of Infancy
Freilich, E. R., Jones, J. M., Gaillard, W. D., Conry, J. A., Tsuchida, T. N., Reyes, C., Dib‐Hajj, S. D., Waxman, S. G., Meisler, M. H., & Pearl, P. L. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.98 · Cited by 93 · see citing works
Genotype phenotype associations across the voltage-gated sodium channel family
Brunklaus, A., Ellis, R., Reavey, E., Semsarian, C., & Zuberi, S. M. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102608 · Cited by 92 · see citing works
Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype
Waxman, S. G. (2007) · Nature Neuroscience · doi:10.1038/nn1857 · Cited by 90 · see citing works
Ramírez, A., Vázquez-Sánchez, A. Y., Carrión-Robalino, N., & Camacho, J. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3928714 · Cited by 89 · see citing works
Xu, R., Thomas, E. A., Jenkins, M., Gazina, E. V., Chiu, C., Heron, S. E., Mulley, J. C., Scheffer, I. E., Berkovic, S. F., & Petrou, S. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.03.003 · Cited by 84 · see citing works
Tatsukawa, T., Raveau, M., Ogiwara, I., Hattori, S., Miyamoto, H., Mazaki, E., Itohara, S., Miyakawa, T., Montal, M., & Yamakawa, K. (2019) · Molecular Autism · doi:10.1186/s13229-019-0265-5 · Cited by 84 · see citing works
Self-citationHirose, S. (2006) · Epilepsy Research · doi:10.1016/j.eplepsyres.2005.12.007 · Cited by 82 · see citing works
Shin, W., Kweon, H., Kang, R., Kim, D., Kim, K., Kang, M., Kim, S. Y., Hwang, S. N., Kim, J. Y., Yang, E., et al. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00145 · Cited by 78 · see citing works
Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy
Madia, F., Striano, P., Gennaro, E., Malacarne, M., Paravidino, R., Biancheri, R., Budetta, M., Cilio, M. R., Gaggero, R., Pierluigi, M., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000238513.70878.54 · Cited by 78 · see citing works
Precision 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
Ji, L., Chauhan, A., Brown, W. T., & Chauhan, V. (2009) · Life Sciences · doi:10.1016/j.lfs.2009.10.008 · Cited by 72 · see citing works
Baasch, A., Hüning, I., Gilissen, C., Klepper, J., Veltman, J. A., Gillessen‐Kaesbach, G., Hoischen, A., & Lohmann, K. (2014) · Epilepsia · doi:10.1111/epi.12554 · Cited by 72 · see citing works
Sodium channel dysfunction in intractable childhood epilepsy with generalized tonic–clonic seizures
Rhodes, T. H., Vanoye, C. G., Ohmori, I., Ogiwara, I., Yamakawa, K., & George, A. L. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.094326 · Cited by 72 · see citing works
Self-citationEpileptogenic Channelopathies: Experimental Models of Human Pathologies
AVANZINI, G., Franceschetti, S., & Mantegazza, M. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01067.x · Cited by 71 · see citing works
Ademuwagun, I. A., Rotimi, S. O., Syrbe, S., Ajamma, Y. U., & Adebiyi, E. F. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.600050 · Cited by 68 · see citing works
Contribution of voltage‐gated sodium channels to the b‐wave of the mammalian flash electroretinogram
Mojumder, D. K., Sherry, D. M., & Frishman, L. J. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.150755 · Cited by 68 · see citing works
Middleton, S. J., Kneller Emily, M., Chen, S., Ogiwara, I., Montal, M., Yamakawa, K., & McHugh, T. J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0163-8 · Cited by 67 · see citing works
Self-citationPure haploinsufficiency for Dravet syndrome NaV1.1 (SCN1A) sodium channel truncating mutations
Bechi, G., Scalmani, P., Schiavon, E., Rusconi, R., Franceschetti, S., & Mantegazza, M. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03346.x · Cited by 67 · see citing works
Begemann, A., Acuña, M. A., Zweier, M., Vincent, M., Steindl, K., Bachmann‐Gagescu, R., Hackenberg, A., Abela, L., Plecko, B., Kroell-Seger, J., et al. (2019) · Molecular Medicine · doi:10.1186/s10020-019-0073-6 · Cited by 66 · see citing works
Self-citationDe novo SCN2A splice site mutation in a boy with Autism spectrum disorder
Tavassoli, T., Kolevzon, A. L., Wang, A. T., Curchack, J. T., Halpern, D. B., Schwartz, L., Soffes, S., Bush, L., Grodberg, D., Cai, G., et al. (2014) · BMC Medical Genetics · doi:10.1186/1471-2350-15-35 · Cited by 62 · see citing works
Mishra, V., Karumuri, B. K., Gautier, N. M., Liu, R., Hutson, T. N., Vanhoof‐Villalba, S. L., VLACHOS, I. K., Iasemidis, L. D., & Glasscock, E. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx104 · Cited by 61 · see citing works
Voltage-Gated Sodium Channels: Mutations, Channelopathies and Targets
Andavan, G. S. B., & Lemmens‐Gruber, R. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711794839133 · Cited by 60 · see citing works
Santos-Rebouças, C. B., Rodrigues, N. F., Jensen, L. R., Kuss, A. W., Ribeiro, M. G., Campos, M., dos Santos, J. M., & Pimentel, M. M. G. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.04.065 · Cited by 59 · see citing works
Bend, E. G., Si, Y. C., Stevenson, D. A., Bayrak‐Toydemir, P., Newcomb, T. M., Jørgensen, E. M., & Swoboda, K. J. (2016) · Neurology · doi:10.1212/wnl.0000000000003095 · Cited by 59 · see citing works
Neonatal Epilepsy Syndromes and Generalized Epilepsy with Febrile Seizures Plus (GEFS+)
Scheffer, I. E., Harkin, L. A., Dibbens, L. M., Mulley, J. C., & Berkovic, S. F. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00358.x · Cited by 59 · see citing works
Andrade, D. M. (2009) · Human Genetics · doi:10.1007/s00439-009-0702-1 · Cited by 59 · see citing works
Yamagata, T., Ogiwara, I., Mazaki, E., Yanagawa, Y., & Yamakawa, K. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.08.013 · Cited by 57 · see citing works
Self-citationYe, M., Yang, J., Tian, C., Zhu, Q., Yin, L., Jiang, S., Yang, M., & Shu, Y. (2018) · Scientific Reports · doi:10.1038/s41598-017-17344-8 · Cited by 57 · see citing works
Mutation screening of SCN2A in schizophrenia and identification of a novel loss-of-function mutation
Carroll, L. S., Woolf, R., Ibrahim, Y., Williams, H. J., Dwyer, S., Walters, J., Kirov, G., O’Donovan, M. C., & Owen, M. J. (2016) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000110 · Cited by 54 · see citing works
The Role of the Persistent Sodium Current in Epilepsy
Wengert, E. R., & Patel, M. K. (2020) · Epiliepsy currents/Epilepsy currents · doi:10.1177/1535759720973978 · Cited by 55 · see citing works
Wu, J., Li, Y., & Jiang, R. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004237 · Cited by 54 · see citing works
Autism spectrum disorder and epileptic encephalopathy: common causes, many questions
Srivastava, S., & Şahin, M. (2017) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-017-9202-0 · Cited by 54 · see citing works
Léna, I., & Mantegazza, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-49392-7 · Cited by 53 · see citing works
Wild-type and mutant ferroportins do not form oligomers in transfected cells
Gonçalves, A. S., Muzeau, F., Blaybel, R., Hetet, G., Driss, F., Delaby, C., Canonne‐Hergaux, F., & Beaumont, C. (2006) · Biochemical Journal · doi:10.1042/bj20051682 · Cited by 52 · see citing works
Amiet, C., Gourfinkel‐An, I., Laurent‐Levinson, C., Bodeau, N., Génin, B., Leguern, É., Tordjman, S., & Cohen, D. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-47 · Cited by 53 · see citing works
SCN 2A channelopathies: Mechanisms and models
Hedrich, U. B. S., Lauxmann, S., & Lerche, H. (2019) · Epilepsia · doi:10.1111/epi.14731 · Cited by 49 · see citing works
Brunklaus, A., & Lal, D. (2020) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14519 · Cited by 49 · see citing works
Que, Z., Olivero-Acosta, M. I., Zhang, J., Eaton, M., Tukker, A. M., Chen, X., Wu, J., Xie, J., Xiao, T., Wettschurack, K. W., et al. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0564-21.2021 · Cited by 48 · see citing works
Resurgent and Gating Pore Currents Induced by De Novo SCN2A Epilepsy Mutations
Mason, E. R., Wu, F., Patel, R. R., Xiao, Y., Cannon, S. C., & Cummins, T. (2019) · eNeuro · doi:10.1523/eneuro.0141-19.2019 · Cited by 46 · see citing works
Molecular bases and clinical spectrum of early infantile epileptic encephalopathies
Asher, Y. J. T., & Scaglia, F. (2012) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2012.04.002 · Cited by 45 · see citing works
Kang, J., Shen, W., Lee, M., Gallagher, M. J., & Macdonald, R. L. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2320-10.2010 · Cited by 45 · see citing works
Ishii, A., Kanaumi, T., Sohda, M., Misumi, Y., Zhang, B., Kakinuma, N., Haga, Y., Watanabe, K., Takeda, S., Okada, M., et al. (2014) · Epilepsy Research · doi:10.1016/j.eplepsyres.2013.12.005 · Cited by 43 · see citing works
Lauxmann, S., Boutry‐Kryza, N., Rivier, C., Mueller, S., Hedrich, U. B. S., Maljevic, S., Szepetowski, P., Lerche, H., & Lesca, G. (2013) · Epilepsia · doi:10.1111/epi.12241 · Cited by 43 · see citing works
Sodium Channel Mutations and Epilepsy
Catterall, W. A. (2012) · Oxford University Press eBooks · doi:10.1093/med/9780199746545.003.0052 · Cited by 41 · see citing works
Kotlar, A., Mercer, K. B., Zwick, M. E., & Mullé, J. G. (2015) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2015.10.008 · Cited by 40 · see citing works
Dutta, U. R., Rao, S. N., Pidugu, V. K., Vineeth, V. S., Bhattacherjee, A., Bhowmik, A. D., Ramaswamy, S. K., Singh, K. G., & Dalal, A. B. (2018) · Genomics · doi:10.1016/j.ygeno.2018.07.005 · Cited by 40 · see citing works
Voltage‐gated sodium channels: Action players with many faces
Koopmann, T. T., Bezzina, C. R., & Wilde, A. A. M. (2006) · Annals of Medicine · doi:10.1080/07853890600969072 · Cited by 40 · see citing works
Relationship of electrophysiological dysfunction and clinical severity inSCN2A-related epilepsies
Lauxmann, S., Verbeek, N. E., Liu, Y., Zaichuk, M., Müller, S., Lemke, J. R., van Kempen, M. J. A., Lerche, H., & Hedrich, U. B. S. (2018) · Human Mutation · doi:10.1002/humu.23619 · Cited by 39 · see citing works
Confirming an expanded spectrum of SCN2A mutations: a case series
Matalon, D. R., Goldberg, E. M., Medne, L., & Marsh, E. D. (2014) · Epileptic Disorders · doi:10.1684/epd.2014.0641 · Cited by 37 · see citing works
Association of genes with phenotype in autism spectrum disorder
Nisar, S., Hashem, S., Bhat, A. A., Syed, N., Yadav, S. K., Azeem, M. W., Shahab Uddin, M. S., Bagga, P., Reddy, R. D., & Haris, M. (2019) · Aging · doi:10.18632/aging.102473 · Cited by 37 · see citing works
Saitoh, M., Ishii, A., Ihara, Y., Hoshino, A., Terashima, H., Kubota, M., Kikuchi, K., Yamanaka, G., Amemiya, K., Hirose, S., et al. (2015) · Epilepsy Research · doi:10.1016/j.eplepsyres.2015.08.001 · Cited by 35 · see citing works
Novel Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotypes
Mastrangelo, M. (2015) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2015.04.001 · Cited by 35 · see citing works
Acute encephalopathy with a novel point mutation in the SCN2A gene
Kobayashi, K., Ohzono, H., Shinohara, M., Saitoh, M., Ohmori, I., Ohtsuka, Y., & Mizuguchi, M. (2012) · Epilepsy Research · doi:10.1016/j.eplepsyres.2012.04.016 · Cited by 32 · see citing works
Phenotypes and genotypes in epilepsy with febrile seizures plus
Ito, M., Yamakawa, K., Sugawara, T., Hirose, S., Fukuma, G., & Kaneko, S. (2006) · Epilepsy Research · doi:10.1016/j.eplepsyres.2005.11.028 · Cited by 32 · see citing works
Self-citation
- Authors
- Kamiya, K., Kaneda, M., Sugawara, T., Mazaki, E., Okamura, N., Montal, M., Makita, N., Tanaka, M., Fukushima, K., Fujiwara, T., Inoue, Y., & Yamakawa, K.
- Affiliations
- RIKEN (JP)
- Keio University (JP)
- University of California San Diego (US)
- Hokkaido University (JP)
- RIKEN Center for Brain Science (JP)
- National Epilepsy Center (JP)
- Corresponding author
- Yamakawa, Kazuhiro
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-03-17
- Volume
- 24
- Issue
- 11
- Pages
- 2690-2698
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6729532
- OpenAlex
- W2096680774
- Cited by
- 199
- References
- 49
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 13 · 2018: 10 · 2017: 9 · 2016: 9 · 2015: 11 · 2014: 20 · 2013: 11 · 2012: 10
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Keio University
- National Institutes of Health
- RIKEN
- National Institute of General Medical Sciences (GM-49711, R01GM049711)
- RIKEN Brain Science Institute
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- SCN2A, nonsense mutation, drug-resistant epilepsy, intellectual disability, Dravet syndrome, de novo mutations, dominant negative effect, haploinsufficiency, voltage-gated sodium channels, voltage-dependent inactivation, subcellular localization, cytoskeletal interactions, focal epilepsy
- MeSH terms
- Adult, Autistic Disorder, Cell Line, DNA Mutational Analysis, Electroencephalography, Epilepsy, Female, Genes, Dominant, Humans, Hyperkinesis, Kidney, Intellectual Disability, Nerve Tissue Proteins, Pedigree, Transfection, Sodium Channels, Gene Expression, Codon, Nonsense, Patch-Clamp Techniques, Protein Subunits, NAV1.2 Voltage-Gated Sodium Channel
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