SCN1A

Species Homo sapiens
Alternate Name(s) NAC1, SCN1, HBSCI, GEFSP2
Epilepsy-Associated Disorder(s) generalized epilepsy with febrile seizures, severe myoclonic epilepsy of infancy (Dravet syndrome)
Description sodium channel, voltage-gated, type I, alpha
Chromosome 2
Locus 2q24.3
Reference(s) Abou-Khalil B, Ge Q, Desai R, Ryther R, Bazyk A, Bailey R, Haines JL, Sutcliffe JS, George AL Jr. Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation. Neurology. 2001 Dec 26;57(12):2265-72.

Annesi G, Gambardella A, Carrideo S, Incorpora G, Labate A, Pasqua AA, Civitelli D, Polizzi A, Annesi F, Spadafora P, Tarantino P, Ciro Candiano IC, Romeo N, De Marco EV, Ventura P, LePiane E, Zappia M, Aguglia U, Pavone L, Quattrone A. Two novel SCN1A missense mutations in generalized epilepsy with febrile seizures plus. Epilepsia. 2003 Sep;44(9):1257-8.

Barela AJ, Waddy SP, Lickfett JG, Hunter J, Anido A, Helmers SL, Goldin AL, Escayg A. An epilepsy mutation in the sodium channel SCN1A that decreases channel excitability. J Neurosci. 2006 Mar 8;26(10):2714-23.

Baulac S, Gourfinkel-An I, Picard F, Rosenberg-Bourgin M, Prud'homme JF, Baulac M, Brice A, LeGuern E. A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33. Am J Hum Genet. 1999 Oct;65(4):1078-85.

Baulac S, Gourfinkel-An I, Couarch P, Depienne C, Kaminska A, Dulac O, Baulac M, LeGuern E, Nabbout R. A novel locus for generalized epilepsy with febrile seizures plus in French families. Arch Neurol. 2008 Jul;65(7):943-51.Click here to read

Bonanni P, Malcarne M, Moro F, Veggiotti P, Buti D, Ferrari AR, Parrini E, Mei D, Volzone A, Zara F, Heron SE, Bordo L, Marini C, Guerrini R. Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven Italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations. Epilepsia. 2004 Feb;45(2):149-58.

Chou IC, Peng CT, Tsai FJ, Huang CC, Shi YR, Tsai CH. The lack of association between febrile convulsions and polymorphisms in SCN1A. Epilepsy Res. 2003 Apr;54(1):53-7.

Clancy CE, Kass RS. Theoretical investigation of the neuronal Na+ channel SCN1A: abnormal gating and epilepsy. Biophys J. 2004 Apr;86(4):2606-14.

Claes L, Ceulemans B, Audenaert D, Smets K, Lofgren A, Del-Favero J, Ala-Mello S, Basel-Vanagaite L, Plecko B, Raskin S, Thiry P, Wolf NI, Van Broeckhoven C, De Jonghe P. De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancy. Hum Mutat. 2003 Jun;21(6):615-21.

Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet. 2001 Jun;68(6):1327-32. Epub 2001 May 15.

Cossette P, Loukas A, Lafreniere RG, Rochefort D, Harvey-Girard E, Ragsdale DS, Dunn RJ, Rouleau GA. Functional characterization of the D188V mutation in neuronal voltage-gated sodium channel causing generalized epilepsy with febrile seizures plus (GEFS). Epilepsy Res. 2003 Feb;53(1-2):107-17.

Davidsson J, Collin A, Olsson ME, Lundgren J, Soller M. Deletion of the SCN gene cluster on 2q24.4 is associated with severe epilepsy: an array-based genotype-phenotype correlation and a comprehensive review of previously published cases. Epilepsy Res. 2008 Sep;81(1):69-79. Epub 2008 Jun 9.Click here to read

Escayg A, Heils A, MacDonald BT, Haug K, Sander T, Meisler MH. A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy. Am J Hum Genet. 2001 Apr;68(4):866-73. Epub 2001 Mar 14.

Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, Brice A, LeGuern E, Moulard B, Chaigne D, Buresi C, Malafosse A. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nat Genet. 2000 Apr;24(4):343-5.

Fukuma G, Oguni H, Shirasaka Y, Watanabe K, Miyajima T, Yasumoto S, Ohfu M, Inoue T, Watanachai A, Kira R, Matsuo M, Muranaka H, Sofue F, Zhang B, Kaneko S, Mitsudome A, Hirose S. Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB). Epilepsia. 2004 Feb;45(2):140-8.

Gennaro E, Veggiotti P, Malacarne M, Madia F, Cecconi M, Cardinali S, Cassetti A, Cecconi I, Bertini E, Bianchi A, Gobbi G, Zara F. Familial severe myoclonic epilepsy of infancy: truncation of Nav1.1 and genetic heterogeneity. Epileptic Disord. 2003 Mar;5(1):21-5.

Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, Sadleir LG, Andermann E, Gill D, Farrell K, Connolly M, Stanley T, Harbord M, Andermann F, Wang J, Batish SD, Jones JG, Seltzer WK, Gardner A, Infantile Epileptic Encephalopathy Referral Consortium; Sutherland G, Berkovic SF, Mulley JC, Scheffer IE. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain. 2007 Mar;130(Pt 3):843-52.

Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, Hirose S, Fukuma G, Mitsudome A, Wada K, Kaneko S. Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A. Epilepsy Res. 2002 Jan;48(1-2):15-23.

Kanai K, Hirose S, Oguni H, Fukuma G, Shirasaka Y, Miyajima T, Wada K, Iwasa H, Yasumoto S, Matsuo M, Ito M, Mitsudome A, Kaneko S. Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity. Neurology. 2004 Jul 27;63(2):329-34.

Li N, Zhang J, Guo JF, Yan XX, Xia K, Tang BS.Novel mutation of SCN1A in familial generalized epilepsy with febrile seizures plus. Neurosci Lett. 2010 Aug 23;480(3):211-4.

Lossin C, Rhodes TH, Desai RR, Vanoye CG, Wang D, Carniciu S, Devinsky O, George AL Jr. Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel SCN1A. J Neurosci. 2003 Dec 10;23(36):11289-95.

Lossin C, Wang DW, Rhodes TH, Vanoye CG, George AL Jr. Molecular basis of an inherited epilepsy. Neuron. 2002 Jun 13;34(6):877-84.

Malacarne M, Madia F, Gennaro E, Vacca D, Guney AI, Buono S, Bernardina BD, Gaggero R, Gobbi G, Lispi ML, Malamaci D, Melideo G, Roccella M, Sferro C, Tiberti A, Vanadia F, Vigevano F, Viri F, Vitali MR, Bricarelli FD, Bianchi A, Zara F. Lack of SCN1A mutations in familial febrile seizures. Epilepsia. 2002 May;43(5):559-62.

Mashimo T, Ohmori I, Ouchida M, Ohno Y, Tsurumi T, Miki T, Wakamori M, Ishihara S, Yoshida T, Takizawa A, Kato M, Hirabayashi M, Sasa M, Mori Y, Serikawa T. A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers susceptibility to febrile seizures in rats. J Neurosci. 2010 Apr 21;30(16):5744-53.

Meisler MH, O'Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. J Physiol. 2010 Jun 1;588(Pt 11):1841-8. Epub 2010 Mar 29.

Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, Capovilla G, Chiron C, Cristofori G, Elia M, Fontana E, Gaggero R, Granata T, Guerrini R, Loi M, La Selva L, Lispi ML, Matricardi A, Romeo A, Tzolas V, Valseriati D, Veggiotti P, Vigevano F, Vallee L, Dagna Bricarelli F, Bianchi A, Zara F. Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology. 2003 Jun 24;60(12):1961-7.

Nabbout R, Kozlovski A, Gennaro E, Bahi-Buisson N, Zara F, Chiron C, Bianchi A, Brice A, Leguern E, Dulac O. Absence of mutations in major GEFS+ genes in myoclonic astatic epilepsy. Epilepsy Res. 2003 Oct;56(2-3):127-33.

Nishri D, Blumkin L, Lev D, Leshinsky-Silver E, Abu-Rashid M, Birch R, Zuberi SM, Lerman-Sagie T. Hepatic coma culminating in severe brain damage in a child with a SCN1A mutation. Eur J Paediatr Neurol. 2010 Apr 12.

Ohmori I, Ouchida M, Ohtsuka Y, Oka E, Shimizu K. Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy. Biochem Biophys Res Commun. 2002 Jul 5;295(1):17-23.

Pineda-Trujillo N, Carrizosa J, Cornejo W, Arias W, Franco C, Cabrera D, Bedoya G, Ruiz-Linares A. A novel SCN1A mutation associated with severe GEFS+ in a large South American pedigree. Seizure. 2005 Mar;14(2):123-8.

Rhodes TH, Lossin C, Vanoye CG, Wang DW, George AL Jr. Noninactivating voltage-gated sodium channels in severe myoclonic epilepsy of infancy. Proc Natl Acad Sci U S A. 2004 Jul 19 [Epub ahead of print].

Selmer KK, Lund C, Brandal K, Undlien DE, Brodtkorb E. SCN1A mutation screening in adult patients with Lennox-Gastaut syndrome features. Epilepsy Behav. 2009 Nov;16(3):555-7.

Shi X, Yasumoto S, Nakagawa E, Fukasawa T, Uchiya S, Hirose S. Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome. Brain Dev. 2009 Nov;31(10):758-62

Spampanato J, Aradi I, Soltesz I, Goldin AL. Increased neuronal firing in computer simulations of sodium channel mutations that cause generalized epilepsy with febrile seizures plus. J Neurophysiol. 2004 May;91(5):2040-50. Epub 2003 Dec 31.

Spampanato J, Escayg A, Meisler MH, Goldin AL. Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2. J Neurosci. 2001 Oct 1;21(19):7481-90.

Spampanato JP, Kearney JA, de Haan G, McEwen DP, Escayg A, Aradi I, MacDonald BT, Levin SI, Soltesz I, Benna P, Montalenti E, Isom LL, Goldin AL, Meisler MH. A Novel Epilepsy Mutation in the Sodium Channel SCN1A Identifies a Cytoplasmic Domain for Subunit Interaction. J. Neurosci. 2004;24(44): 10022-10034.

Specchio N, Trivisano M, Balestri M, Gennaro E, Specchio LM, Fusco L, Zara F, Vigevano F. A novel de novo SCN1A missense mutation in Severe Myoclonic Epilepsy Borderland. Acta Neurol Belg. 2010 Sep;110(3):281-3.

Sugawara T, Mazaki-Miyazaki E, Fukushima K, Shimomura J, Fujiwara T, Hamano S, Inoue Y, Yamakawa K. Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy. Neurology. 2002 Apr 9;58(7):1122-4.

Sugawara T, Tsurubuchi Y, Fujiwara T, Mazaki-Miyazaki E, Nagata K, Montal M, Inoue Y, Yamakawa K. Nav1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents. Epilepsy Res. 2003 May;54(2-3):201-7.

Takayanagi M, Haginoya K, Umehara N, Kitamura T, Numata Y, Wakusawa K, Hino-Fukuyo N, Mazaki E, Yamakawa K, Ohura T, Ohtake M. Acute encephalopathy with a truncation mutation in the SCN1A gene: a case report. Epilepsia. 2010 Sep;51(9):1886-8.

Wallace RH, Hodgson BL, Grinton BE, Gardiner RM, Robinson R, Rodriguez-Casero V, Sadleir L, Morgan J, Harkin LA, Dibbens LM, Yamamoto T, Andermann E, Mulley JC, Berkovic SF, Scheffer IE. Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms. Neurology. 2003 Sep 23;61(6):765-769.

Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, Lerman-Sagie T, Lev D, Mazarib A, Brand N, Ben-Zeev B, Goikhman I, Singh R, Kremmidiotis G, Gardner A, Sutherland GR, George AL Jr, Mulley JC, Berkovic SF. Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet. 2001 Apr;68(4):859-65. Epub 2001 Mar 13.

Weale ME, Depondt C, Macdonald SJ, Smith A, Lai PS, Shorvon SD, Wood NW, Goldstein DB. Selection and evaluation of tagging SNPs in the neuronal-sodium-channel gene SCN1A: implications for linkage-disequilibrium gene mapping. Am J Hum Genet. 2003 Sep;73(3):551-65. Epub 2003 Jul 29.

Weiss LA, Escayg A, Kearney JA, Trudeau M, MacDonald BT, Mori M, Reichert J, Buxbaum JD, Meisler MH. Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol Psychiatry. 2003 Feb;8(2):186-94.

Yao C, Williams AJ, Hartings JA, Lu XC, Tortella FC, Dave JR. Down-regulation of the sodium channel Na(v)1.1 alpha-subunit following focal ischemic brain injury in rats: In situ hybridization and immunohistochemical analysis. Life Sci. 2005 May 4; [Epub ahead of print].

Zhang C, Wong V, Ng PW, Lui CH, Sin NC, Wong KS, Baum L, Kwan P. Failure to detect association between polymorphisms of the sodium channel gene SCN1A and febrile seizures in Chinese patients with epilepsy. Epilepsia. 2010 Sep;51(9):1878-81


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