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SCN8A Publications & References
Bunton-Stasyshyn, Rosie K A, and Jacy L Wagnon. Prominent Role of Forebrain Excitatory Neurons in SCN8A Encephalopathy. Brain, vol. 142, no. 2, 2019, pp. 362–375., doi:10.1093/brain/awy324.
Jain, Puneet, et al. 'Breath Holding Spells' in a Child with SCN8A-Related Epilepsy: Expanding the Clinical Spectrum. Seizure, vol. 65, 2019, pp. 129–130., doi:10.1016/j.seizure.2019.01.020.
Shrourou, Alina. Study uncovers 11 new genes associated with epilepsy. News Medical. 10 Dec. 2018. AZoNetwork. 16 Jan. 2019.
Sojo, L E, et al. On the Feasibility of Quantifying Sodium Channel Nav 1.6 Protein in Mouse Brain Using Targeted UHPLC-ESI- MRM Mass Spectrometry. Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 6 Feb. 2019,
Genome-Wide Mega-Analysis Identifies 16 Loci and Highlights Diverse Biological Mechanisms in the Common Epilepsies. Nature Communications, vol. 9, no. 1, 10 Dec. 2018, doi:10.1038/s41467-018-07524-z.
Human Induced Pluripotent Stem Cell-Derived MGE Cell Grafting after Status Epilepticus Attenuates Chronic Epilepsy and Comorbidities via Synaptic Integration. Proceedings of the National Academy of Sciences, vol. 116, no. 1, 2018, pp. 287–296., doi:10.1073/pnas.1814185115.
Ives, James. Scientists work on better and permanent treatment for epilepsy. News Medical. 21 Dec. 2018. AZoNetwork. 16 Jan. 2019.
Lagae, Lieven, et al. A pilot, open‐label study of the effectiveness and tolerability of low‐dose ZX 008 (fenfluramine HC l) in Lennox‐Gastaut syndrome. Epilepsia 59.10 (2018): 1881-1888.
Liu, Jing, et al. Novel and de novo mutations in pediatric refractory epilepsy. Molecular brain 11.1 (2018): 48.
Ye, Mingyu. Differential Roles of NaV1.2 and NaV1.6 in Regulating Neuronal Excitability at Febrile Temperature and Distinct Contributions to Febrile Seizures. Scientific Reports, vol. 8, no. 1, 2018, doi:10.1038/s41598-017-17344-8.
Braakman HM, Verhoeven JS, Erasmus CE, Haaxma CA, Willemsen MH, Schelhaas HJ. Phenytoin as a last‐resort treatment in SCN8A encephalopathy. Epilepsia Open. 2017;2(3):343-344. doi:10.1002/epi4.12059.
Dallérac G, Moulard J, Benoist J-F, et al. Non-ketogenic combination of nutritional strategies provides robust protection against seizures. Scientific Reports. 2017;7:5496. doi:10.1038/s41598-017-05542-3
Fung C, Kwong AK, Wong VC. Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic encephalopathy. Epilepsia Open. 2017;2(2):236-243. doi:10.1002/epi4.12055.
G. Avanzini, et al., The impact of genetic and experimental studies on classification and therapy of the epilepsies, Neurosci. Lett. (2017),
González‐Cabrera C, Meza R, Ulloa L, et al. Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons. J Comp Neurol. 2017;525:3529–3542.
Johnson KW, Herold KF, Milner TA, Hemmings Jr. HC, Platholi J. Sodium channel subtypes are differentially localized to pre‐ and post‐synaptic sites in rat hippocampus. J Comp Neurol. 2017;525:3563–3578.
Lopez-Santiago LF, Yuan Y, Wagnon JL, Hull JM, Frasier CR, O'Malley HA, Meisler MH, Isom LL. Proc Natl Acad Sci U S A. 2017 Feb 13. pii: 201616821. doi: 10.1073/pnas.1616821114
Makinson et al., Regulation of Thalamic and Cortical Network Synchrony by SCN8A, Neuron (2017), 10.1016/j.neuron.2017.01.031
Markus Wolff et al., Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders, Brain (2017), Volume 140, Issue 5, 1316–1336
Ottolini M, Barker BS, Gaykema RP, Meisler MH, Patel MK. Aberrant sodium channel currents and hyperexcitability of medial entorhinal cortex neurons in a mouse model of SCN8A encephalopathy. J Neurosci. 2017 Jul 4. pii: 2709-16. doi: 10.1523/JNEUROSCI.2709-16.2017.
Symonds JD, Zuberi SM, Johnson MR. Curr Opin Neurol. 2017 Feb 15. doi: 10.1097/WCO.0000000000000433
Tim Rolvien, Sebastian Butscheidt, Anke Jeschke, Axel Neu, Jonas Denecke, Christian Kubisch, Miriam H. Meisler, Klaus Pueschel, Florian Barvencik, Timur Yorgan, Ralf Oheim, Thorsten Schinke, Michael Amling, Severe bone loss and multiple fractures in -related epileptic encephalopathy, Bone, Volume 103, 2017, Pages 136-143, ISSN 8756-3282,
Yangyang Xiao, Jie Xiong, Ding’an Mao, Lingjuan Liu, Jian Li, Xingfang Li, Haiyan Luo, Liqun Liu, Early-onset epileptic encephalopathy with de novo SCN8A mutation, In Epilepsy Research, Volume 139, 2018, Pages 9-13, ISSN 0920-1211,
Zhu H, Lin W, Zhao Y, Wang Z, Lao W, Kuang P, Zhou H. Transient upregulation of Nav1.6 expression in the genu of corpus callosum following middle cerebral artery occlusion in the rats, Brain Research Bulletin, Volume 132, 2017, Pages 20-27, ISSN 0361-9230, (
Barker, B. S., Ottolini, M., Wagnon, J. L., Hollander, R. M., Meisler, M. H. and Patel, M. K. (2016), The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin. Epilepsia. doi: 10.1111/epi.13461
Chad R. Frasier, Jacy L. Wagnon, Yangyang Oliver Bao, Luke G. McVeigh, Luis F. Lopez-Santiago, Miriam H. Meisler, and Lori L. Isom. Cardiac arrhythmia in a mouse model of sodium channel SCN8A epileptic encephalopathy. PNAS 2016 ; published ahead of print October 26, 2016, doi:10.1073/pnas.1612746113.
Gardella E, Becker F, Møller RS, Schubert J, Lemke JR, et al: Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation. Ann Neurol 79:428-436 (2016).
Hammer MF, Wagnon JL, Mefford HC, et al. SCN8A-Related Epilepsy with Encephalopathy. 2016 Aug 25. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from:
Helbig, I., Heinzen, E. L., Mefford, H. C., the ILAE Genetics Commission (2016), Primer Part 1—The building blocks of epilepsy genetics. Epilepsia, 57: 861–868. doi: 10.1111/epi.13381
Horvath G. A., Demos M., Shyr C., Matthews A., Zhang L., Race S., et al. . (2016). Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: a potential treatment target? Mol. Genet. Metab. 117, 42–48. 10.1016/j.ymgme.2015.11.008
Malcolmson J, Kleyner R, Tegay D, et al. SCN8A mutation in a child presenting with seizures and developmental delays. Cold Spring Harbor Molecular Case Studies. 2016;2(6):a001073. doi:10.1101/mcs.a001073.
McNally MA, Johnson J, Huisman TAGM, Poretti A, Baranano K,Baschat AA, Stafstrom CE, SCN8A epileptic encephalopathy: Detection of fetal seizures guidesmultidisciplinary approach to diagnosis and treatment, Pediatric Neurology (2016), doi: 10.1016/j.pediatrneurol.2016.08.003.
Meisler, M. H., Helman, G., Hammer, M. F., Fureman, B. E., Gaillard, W. D., Goldin, A. L., Hirose, S., Ishii, A., Kroner, B. L., Lossin, C., Mefford, H. C., Parent, J. M., Patel, M., Schreiber, J., Stewart, R., Whittemore, V., Wilcox, K., Wagnon, J. L., Pearl, P. L., Vanderver, A. and Scheffer, I. E. (2016), SCN8A encephalopathy: Research progress and prospect. Epilepsia, 57: 1027–1035. doi: 10.1111/epi.13422
Petty, S. J., Milligan, C. J., Todaro, M., Richards, K. L., Kularathna, P. K., Pagel, C. N., French, C. R., Hill-Yardin, E. L., O'Brien, T. J., Wark, J. D., Mackie, E. J. and Petrou, S. (2016), The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts. Epilepsia. doi: 10.1111/epi.13474
Trump N, McTague A, Brittain H, et al. Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis. Journal of Medical Genetics. 2016;53(5):310-317. doi:10.1136/jmedgenet-2015-103263.
Berghuis B, de Kovel CG, van Iterson L, Lamberts RJ, Sander JW, Lindhout D, Koeleman BP. Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy. Epilepsy Res., 115:141-4, 2015.
Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans MC, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels RJ, Meisler MH, Kamsteeg EJ. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. J Med Genet. 52:330-7; 2015.
Deciphering Developmental Disorders S. Large-scale discovery of novel genetic causes of developmental disorders. Nature. 519:223-8; 2015.
Dyment DA, Tetreault M, Beaulieu CL, Hartley T, Ferreira P, Chardon JW, Marcadier J, Sawyer SL, Mosca SJ, Innes AM, Parboosingh JS, Bulman DE, Schwartzentruber J, Majewski J, Tarnopolsky M, Boycott KM, Consortium FC, Care4Rare C. Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study. Clin Genet. 88:34-40.; 2015.
Fung LW, Kwok SL, Tsui KW. SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability. Epilepsia. 56:1319-20; 2015.
Kong W, Zhang Y, Gao Y, Liu X, Gao K, Xie H, Wang J, Wu Y, Zhang Y, Wu X, Jiang Y. SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability. Epilepsia. 56:431-8; 2015.
Larsen J, Carvill GL, Gardella E, Kluger G, Schmiedel G, Barisic N, Depienne C, Brilstra E, Mang Y, Nielsen JE, Kirkpatrick M, Goudie D, Goldman R, Jahn JA, Jepsen B, Gill D, Docker M, Biskup S, McMahon JM, Koeleman B, Harris M, Braun K, de Kovel CG, Marini C, Specchio N, Djemie T, Weckhuysen S, Tommerup N, Troncoso M, Troncoso L, Bevot A, Wolff M, Hjalgrim H, Guerrini R, Scheffer IE, Mefford HC, Moller RS, Euro ERESCCRP. The phenotypic spectrum of SCN8A encephalopathy. Neurology. 84:480-9; 2015.
McMichael G, Bainbridge MN, Haan E, Corbett M, Gardner A, Thompson S, van Bon BW, van Eyk CL, Broadbent J, Reynolds C, O'Callaghan ME, Nguyen LS, Adelson DL, Russo R, Jhangiani S, Doddapaneni H, Muzny DM, Gibbs RA, Gecz J, MacLennan AH. Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy. Mol Psychiatry. 20:176-82; 2015.
Mercimek-Mahmutoglu S, Patel J, Cordeiro D, Hewson S, Callen D, Donner EJ, Hahn CD, Kannu P, Kobayashi J, Minassian BA, Moharir M, Siriwardena K, Weiss SK, Weksberg R, Snead OC, 3rd. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia. 56:707-16; 2015.
Olson HE, Tambunan D, LaCoursiere C, Goldenberg M, Pinsky R, Martin E, Ho E, Khwaja O, Kaufmann WE, Poduri A. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. Am J Med Genet A. 167:2017-25; 2015.
Singh R, Jayapal S, Goyal S, Jungbluth H, Lascelles K. Early-onset movement disorder and epileptic encephalopathy due to de novo dominant SCN8A mutation. Seizure. 26:69-71; 2015.
de Kovel CG, Meisler MH, Brilstra EH, van Berkestijn FM, van 't Slot R, van Lieshout S, Nijman IJ, O'Brien JE, Hammer MF, Estacion M, Waxman SG, Dib-Hajj SD, Koeleman BP. Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy. Epilepsy Res. 108:1511-8; 2014;
Estacion M, O'Brien JE, Conravey A, Hammer MF, Waxman SG, Dib-Hajj SD, Meisler MH. A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel activation in a child with epileptic encephalopathy. Neurobiol Dis. 69:117-23; 2014.
Ohba C, Kato M, Takahashi S, Lerman-Sagie T, Lev D, Terashima H, Kubota M, Kawawaki H, Matsufuji M, Kojima Y, Tateno A, Goldberg-Stern H, Straussberg R, Marom D, Leshinsky-Silver E, Nakashima M, Nishiyama K, Tsurusaki Y, Miyake N, Tanaka F, Matsumoto N, Saitsu H. Early onset epileptic encephalopathy caused by de novo SCN8A mutations. Epilepsia. 55:994-1000; 2014.
Vaher U, Noukas M, Nikopensius T, Kals M, Annilo T, Nelis M, Ounap K, Reimand T, Talvik I, Ilves P, Piirsoo A, Seppet E, Metspalu A, Talvik T. De novo SCN8A mutation identified by whole-exome sequencing in a boy with neonatal epileptic encephalopathy, multiple congenital anomalies, and movement disorders. J Child Neurol. 29:NP202-6; 2014.
Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Moller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet. 45:825-30; 2013.
Epi4k C, Epilepsy Phenome/Genome P, Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR. De novo mutations in epileptic encephalopathies. Nature. 501:217-21; 2013.
O'Brien JE, Meisler MH. Sodium channel SCN8A (Nav1.6): properties and de novo mutations in epileptic encephalopathy and intellectual disability. Front Genet. 4:213; 2013.
Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Ropke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schrock E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet. 380:1674-82; 2012.
Veeramah KR, O'Brien JE, Meisler MH, Cheng X, Dib-Hajj SD, Waxman SG, Talwar D, Girirajan S, Eichler EE, Restifo LL, Erickson RP, Hammer MF. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am J Hum Genet. 90:502-10; 2012.