Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development
Open accessAbstract
Channelopathies are disorders caused by abnormal ion channel function in differentiated excitable tissues. We discovered a unique neurodevelopmental channelopathy resulting from pathogenic variants in SCN3A, a gene encoding the voltage-gated sodium channel Na V 1.3. Pathogenic Na V 1.3 channels showed altered biophysical properties including increased persistent current. Remarkably, affected individuals showed disrupted folding (polymicrogyria) of the perisylvian cortex of the brain but did not typically exhibit epilepsy; they presented with prominent speech and oral motor dysfunction, implicating SCN3A in prenatal development of human cortical language areas. The development of this disorder parallels SCN3A expression, which we observed to be highest early in fetal cortical development in progenitor cells of the outer subventricular zone and cortical plate neurons and decreased postnatally, when SCN1A (Na V 1.1) expression increased. Disrupted cerebral cortical folding and neuronal migration were recapitulated in ferrets expressing the mutant channel, underscoring the unexpected role of SCN3A in progenitor cells and migrating neurons.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The association of SCN3A pathogenic variants with MCD reflects a key role for sodium conductance in cortical progenitors, which affects cortical gyration during early brain development.
“The association of SCN3A pathogenic variants with MCD 37 , therefore, reflects a key role for sodium conductance in cortical progenitors, which affects cortical gyration during early brain development 39 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [39]
The Results and Discussion report that pathogenic SCN3A variants alter sodium-channel currents and that expression of a mutant channel disrupts gyrification in developing ferrets. The Abstract also reports high fetal SCN3A expression in cortical progenitor cells. But the paper says altered sodium conductance *might* underlie polymicrogyria; it does not establish that sodium conductance specifically in progenitors causes the gyration changes. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Prevalence and architecture of de novo mutations in developmental disorders
Study, D. D. D. (2017) · Nature · doi:10.1038/nature21062 · Cited by 1,480 · see citing works
Neurogenic radial glia in the outer subventricular zone of human neocortex
Hansen, D. V., Lui, J. H., Parker, P. R. L., & Kriegstein, A. R. (2010) · Nature · doi:10.1038/nature08845 · Cited by 1,388 · see citing works
GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis
LoTurco, J. J., Owens, D. F., Heath, M. J. S., Davis, M. B. E., & Kriegstein, A. R. (1995) · Neuron · doi:10.1016/0896-6273(95)90008-x · Cited by 1,064 · see citing works
Molecular Identity of Human Outer Radial Glia during Cortical Development
Pollen, A. A., Nowakowski, T. J., Chen, J., Retallack, H., Sandoval-Espinosa, C., Nicholas, C. R., Shuga, J., Liu, S. J., Oldham, M. C., Diaz, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.004 · Cited by 908 · see citing works
Cooper, D. N., Krawczak, M., Polychronakos, C., Tyler‐Smith, C., & Kehrer‐Sawatzki, H. (2013) · Human Genetics · doi:10.1007/s00439-013-1331-2 · Cited by 650 · see citing works
Neural progenitors, neurogenesis and the evolution of the neocortex
Florio, M., & Huttner, W. Β. (2014) · Development · doi:10.1242/dev.090571 · Cited by 625 · see citing works
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
Lelieveld, S. H., Reijnders, M. R. F., Pfundt, R., Yntema, H. G., Kamsteeg, E.-J., de Vries, P., de Vries, B. B. A., Willemsen, M. H., Kleefstra, T., Löhner, K., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4352 · Cited by 442 · 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
Beckh, S., Noda, M., Lübbert, H., & Numa, S. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb08534.x · Cited by 361 · see citing works
Congenital bilateral perisylvian syndrome: study of 31 patients
Kuzniecky, R. (1993) · The Lancet · doi:10.1016/0140-6736(93)90363-l · Cited by 325 · see citing works
The Allen Brain Atlas: 5 years and beyond
Jones, A. R., Overly, C. C., & Sunkin, S. M. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2722 · Cited by 322 · see citing works
Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex
Johnson, M. B., Wang, P. P., Atabay, K. D., Murphy, E. A., Doan, R. N., Hecht, J. L., & Walsh, C. A. (2015) · Nature Neuroscience · doi:10.1038/nn.3980 · Cited by 288 · see citing works
Self-citationBen-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
Persistent Sodium Current and Its Role in Epilepsy
Stafstrom, C. E. (2007) · Epiliepsy currents/Epilepsy currents · doi:10.1111/j.1535-7511.2007.00156.x · Cited by 249 · see citing works
Role of emergent neural activity in visual map development
Ackman, J. B., & Crair, M. C. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.11.011 · Cited by 219 · see citing works
Noncanonical Roles of Voltage-Gated Sodium Channels
Black, J. A., & Waxman, S. G. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.012 · Cited by 210 · see citing works
Tissue-specific expression of the RI and RII sodium channel subtypes.
Gordon, D., Merrick, D., Auld, V. J., Dunn, R., Goldin, A. L., Davidson, N., & Catterall, W. A. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.23.8682 · Cited by 176 · see citing works
A Critical Role for Transmembrane Segment IVS6 of the Sodium Channel α Subunit in Fast Inactivation
McPhee, J. C., Ragsdale, D. S., Scheuer, T., & Catterall, W. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.20.12025 · Cited by 174 · see citing works
Regulation of Persistent Na Current by Interactions between β Subunits of Voltage-Gated Na Channels
Aman, T. K., Grieco‐Calub, T. M., Chen, C., Rusconi, R., Slat, E. A., Isom, L. L., & Raman, I. M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4531-08.2009 · Cited by 171 · see citing works
Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy
Holland, K. D., Kearney, J. A., Glauser, T. A., Buck, G., Keddache, M. A., Blankston, J. R., Glaaser, I. W., Kass, R. S., & Meisler, M. H. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2007.12.064 · Cited by 166 · see citing works
Blanchard, M. G., Willemsen, M. H., Walker, J. B., Dib‐Hajj, S. D., Waxman, S. G., Jongmans, M. C. J., Kleefstra, T., van de Warrenburg, B. P. C., Praamstra, P., Nicolai, J., et al. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102813 · Cited by 143 · see citing works
Sontheimer, H. W., & Waxman, S. G. (1993) · Journal of Neurophysiology · doi:10.1152/jn.1993.70.5.1863 · Cited by 135 · see citing works
Voltage-Gated Sodium Channels: Biophysics, Pharmacology, and Related Channelopathies
Galimberti, E. S., Gollob, M. H., & Darbar, D. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00124 · Cited by 130 · see citing works
Polymicrogyria: A common and heterogeneous malformation of cortical development
Stutterd, C., & Leventer, R. J. (2014) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31399 · Cited by 128 · see citing works
Bilateral frontal polymicrogyria
Guerrini, R., Barkovich, A. J., Sztriha, L., & Dobyns, W. B. (2000) · Neurology · doi:10.1212/wnl.54.4.909 · Cited by 122 · see citing works
Self-citationGenetic neurological channelopathies: molecular genetics and clinical phenotypes
Spillane, J. E., Kullmann, D. M., & Hanna, M. G. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2015-311233 · Cited by 116 · see citing works
Brackenbury, W. J., Davis, T. H., Chen, C., Slat, E. A., Detrow, M. J., Dickendesher, T. L., Ranscht, B., & Isom, L. L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5446-07.2008 · Cited by 110 · see citing works
Upregulation of persistent and ramp sodium current in dorsal horn neurons after spinal cord injury
Lampert, A., Hains, B. C., & Waxman, S. G. (2006) · Experimental Brain Research · doi:10.1007/s00221-006-0511-x · Cited by 104 · see citing works
Mutations in <i>SCN3A</i> cause early infantile epileptic encephalopathy
Zaman, T., Helbig, I., Božović, I. B., DeBrosse, S. D., Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25188 · Cited by 102 · see citing works
Self-citationMoore, A. R., Filipovic, R., Mo, Z., Rasband, M. N., Zečević, N., & Antic, S. D. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn206 · Cited by 101 · see citing works
Estación, M., Gasser, A. S., Dib‐Hajj, S. D., & Waxman, S. G. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.04.012 · Cited by 100 · see citing works
Novel SCN3A variants associated with focal epilepsy in children
Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., & Kearney, J. A. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.10.015 · Cited by 96 · see citing works
Rapid and efficient genetic manipulation of gyrencephalic carnivores using in utero electroporation
Kawasaki, H., Iwai, L., & Tanno, K. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-24 · Cited by 88 · see citing works
Antoine, J.-C. G., Cinotti, L., Tilikete, C., Bouhour, F., Camdessanch�, J. P., Confavreux, C., Vighetto, A., Renault‐Mannel, V., Michel, D., & Honnorat, J. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200007)48:1 · Cited by 86 · see citing works
Self-citationPappalardo, L. W., Samad, O. A., Black, J. A., & Waxman, S. G. (2014) · Glia · doi:10.1002/glia.22671 · Cited by 80 · see citing works
Turner, S. J., Mayes, A., Verhoeven, A., Mandelstam, S. A., Morgan, A. T., & Scheffer, I. E. (2015) · Neurology · doi:10.1212/wnl.0000000000001228 · Cited by 77 · see citing works
Developmental language disorder associated with polymicrogyria
Guerreiro, M. M., Hage, S. R. D. V., Guimarães, C. A., Abramides, D. V. M., Fernandes, W. L. M., Pacheco, P. S., Piovesana, A. M. S. G., Montenegro, M. A., & Cendes, F. (2002) · Neurology · doi:10.1212/wnl.59.2.245 · Cited by 74 · see citing works
SCN3A deficiency associated with increased seizure susceptibility
Lamar, T., Vanoye, C. G., Calhoun, J. D., Wong, J. C., Dutton, S. B. B., Jorge, B. S., Velinov, M. T., Escayg, A., & Kearney, J. A. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.02.006 · Cited by 71 · see citing works
Rash, B. G., Ackman, J. B., & RAKIC, P. T. (2016) · Science Advances · doi:10.1126/sciadv.1501733 · Cited by 70 · see citing works
Worster-Drought syndrome, a mild tetraplegic perisylvian cerebral palsy: Review of 47 cases
Clark, M. (2000) · Brain · doi:10.1093/brain/123.10.2160 · Cited by 67 · see citing works
Sun, G., Werkman, T. R., Battefeld, A., Clare, J. J., & Wadman, W. J. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01001.x · Cited by 56 · see citing works
Estación, M., Vohra, B. P. S., Liu, S., Hoeijmakers, J. G. J., Faber, C. G., Merkies, I. S. J., Lauria, G., Black, J. A., & Waxman, S. G. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00195.2015 · Cited by 54 · see citing works
Hurni, N., Kolodziejczak, M., Tomasello, U., Badia, J., Jacobshagen, M., Prados, J., & Dayer, A. G. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx059 · Cited by 38 · see citing works
Persson, A., Estación, M., Ahn, H., Liu, S., Stamboulian-Platel, S., Waxman, S. G., & Black, J. A. (2014) · Glia · doi:10.1002/glia.22728 · Cited by 37 · see citing works
Black, J. A., Westenbroek, R. E., Minturn, J. E., Ransom, B. R., Catterall, W. A., & Waxman, S. G. (1995) · Glia · doi:10.1002/glia.440140208 · Cited by 29 · see citing works
Jansen, A., Leonard, G. T., Bastos, A. C., Esposito-Festen, J. E., Tampieri, D. I., Watkins, K. E., Andermann, F., & Andermann, E. (2005) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2005.01.012 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Mefford HC, Stephens K, Amemiya A, Ledbetter N, Morgan A, Fisher SE, Scheffer I, Hildebrand M, (1993). FOXP2-Related Speech and Language Disorders. 27336128
Cited by
Sorted by citations
Deconstructing cortical folding: genetic, cellular and mechanical determinants
Llinares-Benadero, C., & Borrell, V. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0112-2 · Cited by 243 · 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
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
Ancestry-inclusive dog genomics challenges popular breed stereotypes
Morrill, K. M., Hekman, J. P., Li, X., McClure, J., Logan, B., Goodman, L., Gao, M., Dong, Y., Alonso, M., Carmichael, E., et al. (2022) · Science · doi:10.1126/science.abk0639 · Cited by 196 · see citing works
Epilepsy genetics: clinical impacts and biological insights
Ellis, C. A., Petrovski, S., & Berkovic, S. F. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30269-8 · Cited by 136 · 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
Ion Channel Functions in Early Brain Development
Smith, R. S., & Walsh, C. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2019.12.004 · Cited by 132 · see citing works
Self-citationBuchsbaum, I. Y., & Cappello, S. (2019) · Development · doi:10.1242/dev.163766 · Cited by 128 · see citing works
Developmental and epileptic encephalopathies
Scheffer, I. E., Zuberi, S., Mefford, H. C., Guerrini, R., & McTague, A. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00546-6 · Cited by 128 · see citing works
Mapping the molecular and cellular complexity of cortical malformations
Klingler, E., Francis, F., Jabaudon, D., & Cappello, S. (2021) · Science · doi:10.1126/science.aba4517 · Cited by 122 · see citing works
Neuron–oligodendroglial interactions in health and malignant disease
Taylor, K. R., & Monje, M. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00744-3 · Cited by 101 · see citing works
Zaman, T., Helbig, K. L., Clatot, J., Thompson, C. H., Kang, S. K., Stouffs, K., Jansen, A. E., Verstraete, L., Jacquinet, A., Parrini, E., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25809 · Cited by 94 · see citing works
Maynard, K. R., Tippani, M., Takahashi, Y., Phan, B. N., Hyde, T. M., Jaffe, A. E., & Martinowich, K. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa312 · Cited by 83 · see citing works
Bioelectrical approaches to cancer as a problem of the scaling of the cellular self
Levin, M. G. (2021) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2021.04.007 · Cited by 82 · see citing works
Oberst, P., Agirman, G., & Jabaudon, D. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.03.004 · Cited by 72 · see citing works
Structural basis for modulation of human NaV1.3 by clinical drug and selective antagonist
Li, X., Xu, F., Xu, H., Zhang, S., Gao, Y., Zhang, H., Dong, Y., Zheng, Y., Yang, B., Sun, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28808-5 · Cited by 71 · see citing works
ATP1A2- and ATP1A3- associated early profound epileptic encephalopathy and polymicrogyria
Vetro, A., Nielsen, H. N., Holm, R., Hevner, R. F., Parrini, E., Powis, Z., Møller, R. S., Bellan, C., Simonati, A., Lesca, G., et al. (2021) · Brain · doi:10.1093/brain/awab052 · Cited by 70 · see citing works
Self-citationWhited, J. L., & Levin, M. G. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.06.014 · Cited by 65 · see citing works
Early role for a Na + ,K + -ATPase ( ATP1A3 ) in brain development
Smith, R. S., Florio, M., Akula, S. K., Partlow, J. N., Wang, Y., Hill, R. S., Goldman, M., Mullally, C. D., Reed, N. M., Bello‐Espinosa, L. E., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023333118 · Cited by 62 · see citing works
Self-citationGenetic pathways involved in human speech disorders
den Hoed, J., & Fisher, S. E. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.05.012 · Cited by 62 · see citing works
Sundberg, M., Pinson, H., Smith, R. S., Winden, K. D., Venugopal, P., Tai, D. J. C., Gusella, J. F., Talkowski, M. E., Walsh, C. A., Tegmark, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23113-z · Cited by 55 · see citing works
Self-citationLiang, L., Darbandi, S. F., Pochareddy, S., Gulden, F. O., Gilson, M. C., Sheppard, B. K., Sahagun, A., An, J., Werling, D. M., Rubenstein, J. L. R., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00949-0 · Cited by 59 · see citing works
Panel), E. P. O. P. P. P. A. T. R. (. P., Hernández, A. F., Adriaanse, P., Aldrich, A., Berny, P. J., Čoja, T., Duquesne, S., Focks, A., Marinovich, M., Millet, M., et al. (2021) · EFSA Journal · doi:10.2903/j.efsa.2021.6599 · Cited by 54 · see citing works
Dendritic Integration Dysfunction in Neurodevelopmental Disorders
Nelson, A. D., & Bender, K. J. (2021) · Developmental Neuroscience · doi:10.1159/000516657 · Cited by 52 · see citing works
HCN2 Channel-Induced Rescue of Brain Teratogenesis via Local and Long-Range Bioelectric Repair
Pai, V. P., Cervera, J., Mafé, S., Willocq, V., Lederer, E. K., & Levin, M. G. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00136 · Cited by 53 · see citing works
O’Hara-Wright, M., Mobini, S., & Gonzalez-Cordero, A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.901652 · Cited by 47 · see citing works
Keough, M. B., & Monje, M. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-111020-092702 · Cited by 46 · see citing works
Localized astrogenesis regulates gyrification of the cerebral cortex
Shinmyo, Y., Saito, K., Hamabe‐Horiike, T., Kameya, N., Ando, A., Kawasaki, K., Duong, T. A. D., Sakashita, M., Roboon, J., Hattori, T., et al. (2022) · Science Advances · doi:10.1126/sciadv.abi5209 · Cited by 47 · see citing works
Recent advances in understanding neocortical development
Borrell, V. (2019) · F1000Research · doi:10.12688/f1000research.20332.1 · Cited by 42 · see citing works
Genetic heterogeneity of polymicrogyria: study of 123 patients using deep sequencing
Stutterd, C., Brock, S., Stouffs, K., Fanjul‐Fernández, M., Lockhart, P. J., McGillivray, G., Mandelstam, S. A., Pope, K., Delatycki, M. B., Jansen, A., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa221 · Cited by 40 · see citing works
Voltage‐gated sodium channels in genetic epilepsy: up and down of excitability
Rusina, E., Simonti, M., Duprat, F., Cestèle, S., & Mantegazza, M. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15947 · Cited by 36 · see citing works
A Meta-Analysis of Bioelectric Data in Cancer, Embryogenesis, and Regeneration
Srivastava, P., Kane, A., Harrison, C., & Levin, M. G. (2020) · Bioelectricity · doi:10.1089/bioe.2019.0034 · Cited by 34 · see citing works
Research models of neurodevelopmental disorders: The right model in the right place
Damianidou, E., Mouratidou, L., & Kyrousi, C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1031075 · Cited by 36 · see citing works
Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex
Bella, D. J. D., Domıńguez-Iturza, N., Brown, J. R., & Arlotta, P. (2024) · Neuron · doi:10.1016/j.neuron.2024.04.021 · Cited by 37 · see citing works
A selective NaV1.1 activator with potential for treatment of Dravet syndrome epilepsy
Chow, C. Y., Chin, Y. K. ‐., Ma, L., Undheim, E. A. B., Herzig, V., & King, G. F. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113991 · Cited by 35 · see citing works
De novo ATP1A3 variants cause polymicrogyria
Miyatake, S., Kato, M., Kumamoto, T., Hirose, T., Koshimizu, E., Matsui, T., Takeuchi, H., Doi, H., Hamada, K., Nakashima, M., et al. (2021) · Science Advances · doi:10.1126/sciadv.abd2368 · Cited by 34 · see citing works
Boscia, F., Elkjaer, M. L., Illés, Z., & Kukley, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.685703 · Cited by 33 · see citing works
The Biophysics of Regenerative Repair Suggests New Perspectives on Biological Causation
Levin, M. G. (2020) · BioEssays · doi:10.1002/bies.201900146 · Cited by 34 · see citing works
Ng, A. C., Chahine, M., Scantlebury, M. H., & Appendino, J. P. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12352-x · Cited by 32 · see citing works
Diverse genetic causes of polymicrogyria with epilepsy
Epilepsy Phenome/Genome Project, E. C. (2021) · Epilepsia · doi:10.1111/epi.16854 · Cited by 31 · see citing works
Qian, X., DeGennaro, E. M., Talukdar, M., Akula, S. K., Lai, A., Shao, D. D., Gonzalez, D. M., Marciano, J. H., Smith, R. S., Hylton, N. K., et al. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.09.011 · Cited by 31 · see citing works
Self-citationHeighway, J., Sedó, A., Garg, A., Eldershaw, L., Perreau, V. M., Berecki, G., Reid, C. A., Petrou, S., & Maljevic, S. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105622 · Cited by 32 · see citing works
Shaping Diversity Into the Brain’s Form and Function
Miterko, L. N., Lackey, E. P., Heck, D. H., & Sillitoe, R. V. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00083 · Cited by 27 · see citing works
Aging as a loss of morphostatic information: A developmental bioelectricity perspective
Pio‐Lopez, L., & Levin, M. G. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102310 · Cited by 31 · see citing works
Akula, S. K., Marciano, J. H., Lim, Y., Exposito-Alonso, D., Hylton, N. K., Hwang, G. H., Partlow, J. N., Dominado, N., Bunton-Stasyshyn, R. K. A., Song, J. H. T., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2209964120 · Cited by 28 · see citing works
Self-citationPlazaola‐Sasieta, H., Zhu, Q., Gaitán‐Peñas, H., Rios, M., Estévez, R., & Morey, M. (2019) · Glia · doi:10.1002/glia.23691 · Cited by 29 · see citing works
Intracranial calcifications in childhood: Part 2
Gonçalves, F. G., Caschera, L., Teixeira, S. R., Viaene, A. N., Pinelli, L., Mankad, K., Alves, C., Ortiz-Gonzalez, X. R., Andronikou, S., & Vossough, A. (2020) · Pediatric Radiology · doi:10.1007/s00247-020-04716-y · Cited by 28 · see citing works
Structure and Function of Sodium Channel Nav1.3 in Neurological Disorders
Liao, S., Liu, T., Yang, R., Tan, W., Gu, J., & Deng, M. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01211-w · Cited by 27 · see citing works
How Do Electric Fields Coordinate Neuronal Migration and Maturation in the Developing Cortex?
Medvedeva, V. P., & Pierani, A. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.580657 · Cited by 26 · see citing works
Pai, V. P., & Levin, M. G. (2022) · Wound Repair and Regeneration · doi:10.1111/wrr.13032 · Cited by 25 · see citing works
Mechanisms of infantile epileptic spasms syndrome: What have we learned from animal models?
Ng, A. C., Choudhary, A., Barrett, K. T., Gavrilovici, C., & Scantlebury, M. H. (2023) · Epilepsia · doi:10.1111/epi.17841 · Cited by 24 · see citing works
A matter of space and time: Emerging roles of disease-associated proteins in neural development
Panagiotakos, G., & Pașca, S. P. (2021) · Neuron · doi:10.1016/j.neuron.2021.10.035 · Cited by 24 · see citing works
Pio‐Lopez, L., & Levin, M. G. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103585 · Cited by 23 · see citing works
Molecular drivers of human cerebral cortical evolution
Suzuki, I. (2019) · Neuroscience Research · doi:10.1016/j.neures.2019.05.007 · Cited by 20 · see citing works
Scalise, S., Zannino, C., Lucchino, V., Conte, M. L., Scaramuzzino, L., Cifelli, P., D’Andrea, T., Martinello, K., Fucile, S., Palma, E., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10051075 · Cited by 22 · see citing works
Piggott, B. J., Peters, C. J., He, Y., Huang, X., Younger, S. H., Jan, L. Y., & Jan, Y. N. (2019) · Genes & Development · doi:10.1101/gad.330597.119 · Cited by 22 · see citing works
Park, Y., Hernandez, S., Hernandez, C. O., Schweiger, H. E., Li, H., Voitiuk, K., Dechiraju, H., Hawthorne, N., Muzzy, E. M., Selberg, J. A., et al. (2024) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100686 · Cited by 21 · see citing works
Inuzuka, L. M., Macedo‐Souza, L. I., Della‐Ripa, B., Cabral, K. S. S., Monteiro, F. P., Kitajima, J. P., Godoy, L. F. D. S., Delgado, D. D. S., Kok, F., & Garzón, E. (2019) · Brain and Development · doi:10.1016/j.braindev.2019.09.004 · Cited by 21 · see citing works
Early dorsomedial tissue interactions regulate gyrification of distal neocortex
Chizhikov, V. V., Iskusnykh, I. Y., Steshina, E. Y., Fattakhov, N. S., Lindgren, A., Shetty, A. S., Roy, A., Tole, S., & Millen, K. J. (2019) · Nature Communications · doi:10.1038/s41467-019-12913-z · Cited by 21 · see citing works
Gorman, K. M., Peters, C. H., Lynch, B., Jones, L., Bassett, D. S., King, M. D., Ruben, P. C., & Rosch, R. E. (2021) · Brain Communications · doi:10.1093/braincomms/fcab235 · Cited by 20 · see citing works
Matthews, E. L., Balestrini, S., Sisodiya, S. M., & Hanna, M. G. (2020) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(19)30425-0 · Cited by 20 · see citing works
Bury, L. A. D., Fu, S., & Wynshaw-Boris, A. J. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114862 · Cited by 19 · see citing works
Bedogni, F., & Hevner, R. F. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.686034 · Cited by 18 · see citing works
Karaküçük‐İyidoğan, A., Başaran, E., Tatar, G., & Oruç‐Emre, E. E. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107662 · Cited by 18 · see citing works
Post-Traumatic Trigeminal Neuropathy: Neurobiology and Pathophysiology
Eliav, T., Benoliel, R., & Korczeniewska, O. A. (2024) · Biology · doi:10.3390/biology13030167 · Cited by 16 · see citing works
Tung, A., & Levin, M. G. (2020) · Developmental Biology · doi:10.1016/j.ydbio.2020.01.010 · Cited by 16 · see citing works
RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes
Brownstein, C. A., Smith, R. S., Rodan, L. H., Gorman, M., Hojlo, M. A., Garvey, E. A., Li, J., Cabral, K., Bowen, J. J., Rao, A. S., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01035-y · Cited by 15 · see citing works
Self-citationMcCrimmon, C. M., Toker, D., Pahos, M., Cao, Q., Lozano, K., Lin, J. J., Parent, J. M., Tidball, A. M., Zheng, J., Molnár, L., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116217 · Cited by 15 · see citing works
A Single-Cell Survey of Cellular Heterogeneity in Human Great Saphenous Veins
Sun, Y.-P., Hu, X., Zhang, K., Rao, M., Yin, P.-B., & Dong, R. (2022) · Cells · doi:10.3390/cells11172711 · Cited by 10 · see citing works
Qu, G., Merchant, J. P., Clatot, J., DeFlitch, L., Frederick, D. J., Tang, S., Salvatore, M., Zhang, X., Li, J., Anderson, S. A., et al. (2023) · Brain · doi:10.1093/brain/awad376 · Cited by 15 · see citing works
A hyperthermic seizure unleashes a surge of spreading depolarizations in Scn1a-deficient mice
Aiba, I., Ning, Y. Y., & Noebels, J. L. (2023) · JCI Insight · doi:10.1172/jci.insight.170399 · Cited by 15 · see citing works
Spildrejorde, M., SAMARA, A. A., Sharma, A., Leithaug, M., Falck, M., Modafferi, S., Sundaram, A. Y. M., Acharya, G., Nordeng, H., Eskeland, R., et al. (2023) · iScience · doi:10.1016/j.isci.2023.107755 · Cited by 14 · see citing works
Koch, N. A., Sonnenberg, L., Hedrich, U. B. S., Lauxmann, S., & Benda, J. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1194811 · Cited by 14 · see citing works
The Control of Cortical Folding: Multiple Mechanisms, Multiple Models
Moffat, A., & Schuurmans, C. J. (2023) · The Neuroscientist · doi:10.1177/10738584231190839 · Cited by 12 · see citing works
Shinmyo, Y., Hamabe‐Horiike, T., Saito, K., & Kawasaki, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.847159 · Cited by 11 · see citing works
Mao, M., Mattei, C., Rollo, B., Byars, S., Cuddy, C., Berecki, G., Heighway, J., Pachernegg, S., Menheniott, T. R., Apted, D., et al. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0692-23.2023 · Cited by 15 · see citing works
An Electric Take on Neural Fate and Cortical Development
Lancaster, M. A. (2019) · Developmental Cell · doi:10.1016/j.devcel.2018.12.014 · Cited by 11 · see citing works
Schlusche, A. K., Vay, S. U., Kleinenkuhnen, N., Sandke, S., Campos-Martín, R., Florio, M., Huttner, W. Β., Tresch, A., Roeper, J., Rueger, M. A., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2009393118 · Cited by 11 · see citing works
King, Y.-H. L., Chen, C., King, J. V. L., Simms, J. A., Glasscock, E., Yang, S., Jan, Y. N., & Jan, L. Y. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2118240119 · Cited by 10 · see citing works
Neuronal hyperactivity in neurons derived from individuals with gray matter heterotopia
Matteo, F. D., Bonrath, R., Pravatà, V. M., Schmidt, H., Martin, A. C. A., Giaimo, R. D., Menegaz, D., Riesenberg, S., de Vrij, F. M. S., Maccarrone, G., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56998-1 · Cited by 10 · see citing works
Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants
D’Gama, A. M., Phillips, H. W., Wang, Y., Chiu, M. Y., Chahine, Y., Swanson, A. C., Smith, R. S., Pearl, P. L., Tsuboyama, M., Madsen, J. R., et al. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf113 · Cited by 10 · see citing works
Self-citationPolymicrogyria in a child with KCNMA1-related channelopathy
Graber, D., Imagawa, E., Miyake, N., Matsumoto, N., Miyatake, S., Graber, M., & Isidor, B. (2021) · Brain and Development · doi:10.1016/j.braindev.2021.09.009 · Cited by 10 · see citing works
Lesional and non-lesional epilepsies: A blurring genetic boundary
Guerrini, R., Parrini, E., Esposito, A., Fassio, A., & Conti, V. (2019) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2019.12.013 · Cited by 10 · see citing works
Cortical and subcortical morphological alteration in Angelman syndrome
Du, X., Wei, L., Yang, B., Long, S., Wang, J., Sun, A., Jiang, Y., Qiao, Z., Wang, H., & Wang, Y. (2023) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-022-09469-3 · Cited by 9 · see citing works
Rare dysfunctional SCN2A variants are associated with malformation of cortical development
Clatot, J., Thompson, C. H., Sotardi, S. T., Jiang, J., Trivisano, M., Balestrini, S., Ward, D. I., Ginn, N., Guaragni, B., Malerba, L., et al. (2024) · Epilepsia · doi:10.1111/epi.18234 · Cited by 8 · see citing works
Precision medicine for sodium channelopathy-related autism and epilepsy
Robinson, M. J., Wettschurack, K. W., Halurkar, M. S., Chen, X., Zhang, Z., Zhang, J., & Yang, Y. (2025) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2025.09.007 · Cited by 8 · see citing works
Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes
Aboitiz, F., & Montiel, J. F. (2019) · Evolution & Development · doi:10.1111/ede.12308 · Cited by 8 · see citing works
1-L Transcription in Alzheimer’s Disease
Nahálka, J. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44080243 · Cited by 7 · see citing works
Maintenance of Melanocyte Stem Cell Quiescence by GABA-A Signaling in Larval Zebrafish
Allen, J., Skeath, J. B., & Johnson, S. L. (2019) · Genetics · doi:10.1534/genetics.119.302416 · Cited by 7 · see citing works
Predicting the impact of sodium channel mutations in human brain disease
Noebels, J. L. (2019) · Epilepsia · doi:10.1111/epi.14724 · Cited by 7 · see citing works
The One-Stop Gyrification Station - Challenges and New Technologies
Hickmott, R. A., Bosakhar, A., Quezada, S., Barresi, M., Walker, D. W., Ryan, A. L., Quigley, A. F., & Tolcos, M. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102111 · Cited by 7 · see citing works
Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?
Healy, D., LaPalme, J., & Levin, M. G. (2019) · Bioelectricity · doi:10.1089/bioe.2019.0010 · Cited by 6 · see citing works
Exome hits demystified: The next frontier
Ithal, D., Sukumaran, S. K., Bhattacharjee, D., Vemula, A., Nadella, R. K., Mahadevan, J., Sud, R., Viswanath, B., Purushottam, M., & Jain, S. (2021) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2021.102640 · Cited by 6 · see citing works
SCN3A- Related Neurodevelopmental Disorder
Helbig, K. L., & Goldberg, E. M. (2021) · Europe PMC (PubMed Central) · Cited by 6 · see citing works
Hiraide, T., Akita, T., Uematsu, K., Miyamoto, S., Nakashima, M., Sasaki, M., Fukuda, A., Kato, M., & Saitsu, H. (2022) · Journal of Human Genetics · doi:10.1038/s10038-022-01090-5 · Cited by 6 · see citing works
Kawasaki, H. (2024) · The Journal of Comparative Neurology · doi:10.1002/cne.25615 · Cited by 6 · see citing works
Pattie, E. A., & Iffland, P. H. (2025) · Brain Sciences · doi:10.3390/brainsci16010054 · Cited by 5 · see citing works
Chow, C. Y., & King, G. F. (2024) · Toxins · doi:10.3390/toxins16070307 · Cited by 5 · see citing works
Rewiring Endogenous Bioelectric Circuits in the Xenopus laevis Embryo Model
Nanos, V., & Levin, M. G. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-1174-6_7 · Cited by 5 · see citing works
- Authors
- Smith, R. S., Kenny, C. J., Ganesh, V., Jang, A., Borges-Monroy, R., Partlow, J. N., Hill, R. S., Shin, T., Chen, A. Y., Doan, R. N., Anttonen, A.-K., Ignatius, J., Medne, L., Bönnemann, C. G., Hecht, J. L., Salonen, O., Barkovich, A. J., Poduri, A., Wilke, M., de Wit, M. C. Y., Mancini, G. M. S., Sztriha, L., Im, K., Amrom, D., Andermann, E., Paetau, R., Lehesjoki, A.-E., Walsh, C. A., & Lehtinen, M. K.
- Affiliations
- Boston Children's Hospital (US)
- University of Helsinki (FI)
- Turku University Hospital (FI)
- Children's Hospital of Philadelphia (US)
- Beth Israel Deaconess Medical Center (US)
- University of California, San Francisco (US)
- Erasmus MC (NL)
- Montreal Neurological Institute and Hospital (CA)
- Corresponding author
- Walsh, Christopher A.
- Lehtinen, Maria K.
- ORCID
- Smith, Richard S.
- Kenny, Connor J.
- Jang, Ahram
- Borges-Monroy, Rebeca
- Shin, Taehwan
- Doan, Ryan N.
- Anttonen, Anna-Kaisa
- Ignatius, Jaakko
- Bönnemann, Carsten G.
- Hecht, Jonathan L.
- Barkovich, A. James
- Poduri, Annapurna
- Wilke, Martina
- Mancini, Grazia M.S.
- Im, Kiho
- Amrom, Dina
- Lehesjoki, Anna-Elina
- Walsh, Christopher A.
- Lehtinen, Maria K.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 99
- Issue
- 5
- Pages
- 905-913.e7
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC6226006
- OpenAlex
- W2888053187
- Cited by
- 160
- References
- 47
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 23 · 2023: 21 · 2022: 26 · 2021: 24 · 2020: 18 · 2019: 19 · 2018: 2
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Funders
- NIH (1F32NS100033801, R01NS032457, R01NS035129)
- Erasmus MC Mrace project (#104673)
- Finnish Medical Society
- Arvo and Lea Ylppö Foundation
- Finnish governmental subsidiaries (TLK0278, TRTR019)
- The Folkhälsan Research Foundation
- Paul G. Allen Frontiers Program
- New York Stem Cell Foundation
- BCH IDDRC (1U54HD090255)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- SCN3A, Nav1.3, voltage-gated sodium channels, channelopathies, neurodevelopmental disorders, polymicrogyria, oral motor dysfunction, speech development, neuronal migration, SCN1A, ferret model, persistent sodium current
- MeSH terms
- Adolescent, Adult, Animals, Cell Movement, Cells, Cultured, Cerebral Cortex, Child, Child, Preschool, Female, Ferrets, Humans, Infant, Language Development, Male, Middle Aged, Pedigree, Sodium Channels, HEK293 Cells, Megalencephaly, NAV1.3 Voltage-Gated Sodium Channel, Polymicrogyria
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
