Occurrence and clinical treatment of epilepsy associated with gene mutation in voltagegated sodium channel subtypes

doi:10.12092/j.issn.1009-2501.2018.05.015

Abstract

Abstract:

Epilepsy is a common brain disease caused by abnormal discharge of brain neurons with a characteristic of short brain dysfunction. It can break out repeatedly, and has a serious influence on the health and quality of life of patients. Previous studies have found that voltagegated sodium channel subtypes (Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7) expressed in the central nervous system play an important role in the pathogenesis of epilepsy, and they are targets for related antiepileptic drugs. The mutations in the encoding gene of αsubunit of these channels can cause different forms of epileptic seizures. This paper reviewed the occurrence and clinical treatment of epilepsy related with mutations in the five VGSC subtypes expressed in the central nervous system, providing basis for the studies on electrophysiology mechanism of occurrence and development of epilepsy and clinical treatment.

Key words: voltage gated sodium channel, gene mutation, epilepsy, clinical treatment

CLC Number:

R742.1

TAO Huai, XU Lujiadai, CHEN Xia. Occurrence and clinical treatment of epilepsy associated with gene mutation in voltagegated sodium channel subtypes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 570-577.

References

［1］沈春红, 王爽, 郭谊, 等. 癫痫发生的分子机制研究进展［J］. 中国现代神经疾病杂志, 2012, 12(5): 516-520.
［2］Steinlein OK. Mechanisms underlying epilepsies associated with sodium channel mutations［J］. Prog Brain Res, 2014, 213:97-111.
［3］Baqal SK, Marron BE, Owen RM, et al. Voltage gated sodium channels as drug discovery targets［J］. Channel (Austin), 2015, 9(6): 360-366.
［4］Catterall WA. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels［J］. Neuron, 2000, 26(1): 13-25.
［5］Catterall WA. Structure and function of voltage-gated sodium channels at atomic resolution［J］. Exp Physiol, 2014, 99(1): 35-51.
［6］Payandeh J, Gamal ElDin TM, Scheuer T, et al. Crystal structure of a voltage-gated sodium channel in two potentially inactivated states［J］. Nature, 2012, 486(7401): 135-139.
［7］Goldin AL, Barchi RL, Caldwell JH, et al. Nomenclature of voltage-gated sodium channels［J］. Neuron, 2000, 28(2): 365-368.
［8］Catterall WA, Goldin AL, Waxman SG. International Union of Pharmacology: XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channel［J］. Pharmacol Rev, 2005, 57(4): 397-409.
［9］Ogiwara I, Miyamoto H, Morita N, et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation［J］. J Neurosci, 2007, 27(22): 5903-5914.
［10］Meisler MH, O'Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects［J］. J Physiol, 2010, 588: 1841-1848.
［11］Alekov AK, Rahman MM, Mitrovic N, et al. Enhanced inactivation and acceleration of activation of the sodium channel associated with epilepsy in man［J］. Eur J Neurosci, 2001, 13(11): 2171-2176.
［12］Spampanato J, Escayg A, Meisler MH, et al. Functional effects of two voltagegated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2［J］. J Neurosci, 2001, 21(19): 74817490.
［13］Martin MS, Dutt K, Papale LA, et al. Altered function of the SCN1A voltage-gated sodium channel leads to gamma-aminobutyric acid-ergic (GABAergic) inerneuron abnormalities［J］. J Biol Chem, 2010, 285(13): 9823-9834.
［14］Gauthier AC, Manganas LN, Mattson RH. A novel inherite SCN1A mutation associated with GEFS+ in benign and encephalopathic epilepsy［J］. J Clin Neurosci, 2017, 40: 82-84.
［15］Battaglia D, Ricci D, Chieffo D, et al. Outlining a core neuropsychological phenotype for Dravet syndrome［J］. Epilepsy Res, 2016, 120: 91-97.
［16］Hammer MF, Ishii A, Johnstone L, et al. Rare variants of small effect size in neuronal excitability genes influence clinical outcome in Japanese cases of SCN1A truncation-positive Dravet syndrome［J］. PloS One, 2017, 12(7):e0180485.
［17］Jiménez-Arredondo RE, Brambila-Tapia AJL, Mercado-Silva FM, et al. Determination of SCN1A genetic variants in mexican patients with refractory epilepsy and dravet syndrome［J］. Genet Mol Res, 2017, 16(2). doi: 10.4238/gmr16029405.
［18］Wallace A, Wirrell E, Kenney-Jung DL. Pharmacotherapy for Dravet Syndrome［J］. Paediatr Drugs, 2016, 18(3): 197-208.
［19］Bertok S, Dolan V, Goricar K, et al. The association of SCN1A p. Thr1067Ala polymorphism with epilepsy risk and the response to antiepileptic drugs in Slovenian children and adolescents with epilepsy［J］. Seizure, 2017, 51: 9-13.
［20］Duménieu M, Oulé M, Kreutz MR, et al. The segregated expression of voltage-gated potassium and sodium channels in neuronal membranes: functional implications and regulatory mechanisms［J］. Front Cell Neurosci, 2017, 11: 115.
［21］Baasch AL, Hüning I, Gillissen C, et al. Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intelllectual disability, optic atrophy, muscular hypotonia, and brain abnormalities［J］. Epilepsia, 2014, 55(4): e25-e29.
［22］Sugawara T, Tsurubuchi Y, Agarwala KL, et al. A missense mutation of the Na1 channel aII subunit gene Nav1.2 in a patient with febrile and afebrile seizures causes channel dysfunction［J］. Proc Natl Acad Sci USA, 2001, 98(11): 6384-6389.
［23］Syrbe S, Zhorov BS, Bertsche A, et al. Phenotypic variability from benign infantile epilepsy to ohtahara syndrome associated with a novel mutation in SCN2A［J］. Mol syndromol, 2016, 7(4): 182-188.
［24］Hauk, Hallmann K, Rebstock J, et al. The voltage-gated sodium channel gene SCN2A and idiopathic generalized［J］. Epilepsy Res, 2001, 47(3): 243-246.
［25］Kamiya K, Kaneda M, Sugawara T, et al. A nonsense mutation of the sodium channel gene SCN2A in patient with intractable epilepsy and mental decline［J］. J Neurosci, 2004, 24(11): 2690-2698.
［26］Nakamura K, Kato M, Yamashita S, et al. Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome［J］. Neurology, 2013, 81(11): 992-998.
［27］Ogiwara I, Ito K, Sawaishi Y, et al. De novo mutations of voltage gated sodium channel αII gene SCN2A in intractable epilepsies［J］. Neurology, 2009, 73(13): 1046-1053.
［28］Dilena R, Striano R, Gennaro E, et al. Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy［J］. Brain Dev, 2017, 39(4): 345-348.
［29］Wolff M, Johannesen KM, Hedrich UB, et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2Arelated disorders［J］. Brain, 2017, 140(5): 1316-1336.
［30］Leterrier C, Brachet A, Fache MP, et al. Voltage-gated sodium channel organization in neurons: Protein interactions and trafficking pathways［J］. Neurosci Lett, 2010, 486(2): 92-100.
［31］Holland KD, Kearney JA, Glauser TA, et al. Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy［J］. Neurosci Lett, 2008, 433(1): 65-70.
［32］Vanoye CG, Gurnett CA, Holland KD, et al. Novel SCN3A variants associated with focal epilepsy in children［J］. Neurobiol Dis, 2014, 62(2): 313-322.
［33］Lamar T, Vanoye GG, Calhoun J, et al. SCN3A deficiency associated with increased seizure susceptibility［J］. Neurobiol Dis, 2017, 102: 38-48.
［34］Thuresson AC, Van Buqqenhout G, Sheth F, et al. Whole gene duplication of SCN2A and SCN3A is associated with neonatal seizures and a normal intellectual development［J］. Clin Genet, 2017, 91(1): 106-110.
［35］Yoshitomi S, Takahashi Y, Ishizuka M, et al. Three patients manifestign early infantile epileptic spasms associated with 2q24.3 microduplications［J］. Brain Dev, 2015, 37(9): 874-879.
［36］Lopez-Santiago LF, Yuan Y, Wagnon JL, et al. Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy［J］. Proc Natl Acad Sci USA, 2017, 114(9): 2383-2388.
［37］Larsen J, Carvill GL, Gardella E, et al. The phenotypic spectrum of SCN8A encephalopathy［J］. Neurology, 2015, 84: 480-489.
［38］Papale LA, Beyer B, Jones JM, et al. Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spikewave discharges and absence epilepsy in mice［J］. Hum Mol Genet, 2009, 18(9): 1633-1641.
［39］Oliva MK, McGarr TC, Beyer BJ, et al. Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy［J］. Neurobiol Dis, 2014, 67: 180-190.
［40］Ottolini M, Barker BS, Gaykema RP, et al. Aberrant sodium channel currents and hyperexcitability of medial entorhinal cortex neurons in a mouse model of SCN8A encephalopathy［J］. J Neurosci, 2017, 37(32): 2709-2716.
［41］Lopez-Santiago LF, Yuan Y, Wagnon JL, et al. Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy［J］. Proc Natl Acad Sci USA, 2017, 114(9): 2383-2388.
［42］Boerma RS, Braun KP, van de Broek MP, et al. Remarkable phenytoin sensitivity in 4 children with SCN8A-related epilepsy: A molecular neuropharmacological approach［J］. Neurotherapeutics, 2016, 13: 192-197.
［43］Puneet J. Novel SCN8A mutation in a girl with refractory seizures and autistic features［J］. Neurol India, 2017, 65(1): 180-181.
［44］Mechaly I, Scamps F, Chabbert C, et al. Molecular diversity of voltage gated sodium channel alpha subunits expressed in neuronal and nonneuronal excitable cells［J］. Neuroscience, 2005, 130(2): 389-396.
［45］Singh NA, Pappas C, Dahle EJ, et al. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome［J］. PLoS Genet, 2009, 5(9): e1000649.
［46］Mulley JC, Hodqson B, Mcmahon JM, et al. Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and dravet syndrome［J］. Epilepsia, 2013, 54(9): e122-e126.

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