SCN2A基因突变相关的癫痫研究进展
Research Advances in Epilepsy Related to SCN2A Gene Mutation

DOI: 10.12677/ACREM.2021.92004, PP. 20-24

Keywords: SCN2A基因，癫痫，遗传
SCN2A Gene, Epilepsy, Heredity

Full-Text   Cite this paper   Add to My Lib

Abstract:

SCN2A (Sodium voltage-gated channel alpha subunit 2)基因编码的神经元电压门控钠通道Nav1.2是中枢神经系统表达的四个钠通道类似物之一，在大脑中分布广泛，参与一系列神经元动作电位的启动和传导。SCN2A基因突变所致的癫痫表型谱广，其基因突变类型和临床表型之间有很强的相关性，既可表现为良性预后的癫痫，也可表现为癫痫性脑病。SCN2A基因突变可为遗传性突变或新生突变，且突变类型多样，其中以错义突变最常见。该文就近年来SCN2A基因突变相关的癫痫研究进展进行阐述，总结其临床特征及遗传学特点，为治疗提供新思路。
The neuronal voltage-gated sodium channel Nav1.2 is encoded by SCN2A gene. And it is one of the four sodium channel analogues which expressed in the central nervous system. Nav1.2 is widely distributed in the brain and participates in the initiation and conduction of a series of neuronal action potentials. The epilepsy phenotype caused by SCN2A gene mutations has a wide spectrum, and there is a strong correlation between types of gene mutations and clinical phenotype. And the phenotype can be manifested as epilepsy with benign prognosis or epileptic encephalopathy. The SCN2A gene mutations can be hereditary mutations or de novo mutations, and there are various types of mutations, among which missense mutations are the most common. This article describes the research advance of SCN2A gene mutation related-epilepsy in recent years, summarizes its clinical and genetic characteristics, and provides new ideas for treatment.

References

[1]	Maloney, E.M., Chaila, E., O’Reilly, I.J., et al. (2020) The Incidence of First Seizures, Epilepsy and Seizure Mimics in a Geographically Defined Area. Neurology, 95, e576-e590.
[2]	Hedrich, U., Lauxmann, S. and Lerche, H. (2019) SCN2A Channelopathies: Mechanisms and Models. Epilepsia, 60, S68-S76. https://doi.org/10.1111/epi.14731
[3]	Mason, E.R., Wu, F., et al. (2019) Resurgent and Gating Pore Currents In-duced by De Novo SCN2A Epilepsy Mutations. eNeuro, 6, ENEURO.0141-19. https://doi.org/10.1523/ENEURO.0141-19.2019
[4]	康庆云, 廖红梅, 陈玫, 等. 5例SCN2A基因突变相关癫痫性脑病患儿的临床特征及基因突变分析[J]. 癫痫与神经电生理学杂志, 2020, 29(5): 257-261.
[5]	Reynolds, C., King, M.D. and Gorman, K.M. (2020) The Phenotypic Spectrum of SCN2A-Related Epilepsy. European Journal of Paediatric Neurology, 24, 117-122. https://doi.org/10.1016/j.ejpn.2019.12.016
[6]	Adney, S.K., Millichap, J.J., DeKeyser, J.M., et al. (2020) Functional and Pharmacological Evaluation of a Novel SCN2A Variant Linked to Ear-ly-Onset Epilepsy. Annals of Clinical and Translational Neurology, 7, 1488-1501. https://doi.org/10.1002/acn3.51105
[7]	Begemann, A., Acu？a, M.A., Zweier, M., et al. (2019) Further Corrobora-tion of Distinct Functional Features in SCN2A Variants Causing Intellectual Disability or Epileptic Phenotypes. Molecu-lar Medicine, 25, Article No. 6. https://doi.org/10.1186/s10020-019-0073-6
[8]	Lauxmann, S., Verbeek, N.E., Liu, Y., et al. (2018) Relationship of Electrophysiological Dysfunction and Clinical Severity in SCN2A-Related Epilepsies. Human Mutation, 39, 1942-1956. https://doi.org/10.1002/humu.23619
[9]	Sugawara, T., Tsurubuchi, Y., Agarwala, K.L., et al. (2001) A Missense Mutation of the Na+ Channel Alpha II Subunit Gene Na(v)1.2 in a Patient with Febrile and Afebrile Seizures Causes Channel Dysfunction. Proceedings of the National Academy of Sciences of the United States of America, 98, 6384-6389. https://doi.org/10.1073/pnas.111065098
[10]	Zara, F., Specchio, N., Striano, P., et al. (2013) Genetic Testing in Benign Familial Epilepsies of the First Year of Life: Clinical and Diagnostic Significance. Epilepsia, 54, 425-436. https://doi.org/10.1111/epi.12089
[11]	Nakamura, K., Kato, M., Osaka, H., et al. (2013) Clinical Spec-trum of SCN2A Mutations Expanding to Ohtahara Syndrome. Neurology, 81, 992-998. https://doi.org/10.1212/WNL.0b013e3182a43e57
[12]	Howell, K.B., et al. (2015) SCN2A Encephalopathy a Major Cause of Epilepsy of Infancy with Migrating Focal Seizures. Neurology, 85, 958-966. https://doi.org/10.1212/WNL.0000000000001926
[13]	Wolff, M., Brunklaus, A. and Zuberi, S.M. (2019) Pheno-typic Spectrum and Genetics of SCN2A-Related Disorders, Treatment Options, and Outcomes in Epilepsy and Beyond. Epilepsia, 60, S59-S67. https://doi.org/10.1111/epi.14935
[14]	Wolff, M., Johannesen, K.M., Hedrich, U.B.S., et al. (2017) Genetic and Phenotypic Heterogeneity Suggest Therapeutic Implications in SCN2A-Related Disorders. Brain: A Journal of Neurology, 140, 1316-1336. https://doi.org/10.1093/brain/awx054
[15]	Su, D.J., Lu, J.F., Lin, L.J., et al. (2018) SCN2A Mutation in an Infant Presenting with Migrating Focal Seizures and Infantile Spasm Responsive to a Ketogenic Diet. Brain & Development, 40, 724-727. https://doi.org/10.1016/j.braindev.2018.03.005
[16]	Melikishvili, G., Dulac, O. and Gataullina, S. (2020) Neonatal SCN2A Encephalopathy: A Peculiar Recognizable Electroclinical Sequence. Epilepsy & Behavior, 111, Article ID: 107187. https://doi.org/10.1016/j.yebeh.2020.107187
[17]	Kong, Y., Yan, K., Hu, L., et al. (2018) Association between SCN1A and SCN2A Mutations and Clinical/EEG Features in Chinese Patients from Epilepsy or Severe Sei-zures. Clinica Chimica Acta, 483, 14-19. https://doi.org/10.1016/j.cca.2018.03.027
[18]	Zhou, P., He, N., Zhang, J.W., et al. (2018) Novel Mutations and Phenotypes of Epilepsy-Associated Genes in Epileptic Encephalopathies. Genes, Brain and Behavior, 17, e12456. https://doi.org/10.1111/gbb.12456
[19]	Deborah, J.M. and Marc-Antoine, C. (2020) Neurodevelopmental Disor-ders—The History and Future of a Diagnostic Concept. Dialogues in Clinical Neuroscience, 22, 65-72. https://doi.org/10.31887/DCNS.2020.22.1/macrocq

Full-Text