发育性和癫痫性脑病遗传学病因及诊疗的研究进展

doi:10.16288/j.yczz.23-105

遗传 ›› 2023, Vol. 45 ›› Issue (7): 553-567.doi: 10.16288/j.yczz.23-105

发育性和癫痫性脑病遗传学病因及诊疗的研究进展

金良(), 陈语婕, 陈勇军()

南华大学衡阳医学院附属南华医院神经内科，衡阳 421002

收稿日期:2023-04-19 修回日期:2023-05-21 出版日期:2023-07-20 发布日期:2023-05-31
通讯作者: 陈勇军 E-mail:Jliang811@163.com;chenyj-usc@foxmail.com
作者简介:金良，在读硕士研究生，专业方向：神经遗传性疾病。E-mail: Jliang811@163.com
基金资助:
湖南省卫生健康委重点指导课题(20201910);南华大学临床医学研究“4310”计划项目(20224310NHYCG11)

Advances in genetic etiology, diagnosis and treatment of developmental and epileptic encephalopathy

Liang Jin(), Yujie Chen, Yongjun Chen()

Department of Neurology, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China

Received:2023-04-19 Revised:2023-05-21 Online:2023-07-20 Published:2023-05-31
Contact: Yongjun Chen E-mail:Jliang811@163.com;chenyj-usc@foxmail.com
Supported by:
Support by the Key Project of Hunan Provincial Health and Health Commission(20201910);“4310” Program of Clinical Medical Research of the University of South China(20224310NHYCG11)

摘要/Abstract

摘要：

发育性和癫痫性脑病(developmental and epileptic encephalopathy, DEE)是一组临床和遗传异质的年龄依赖性神经系统疾病，其特征是在婴儿期或儿童早期出现难治性癫痫发作，且受影响的个体有精神运动发育迟缓或倒退。随着二代测序技术的发展，尤其是全外显子测序技术的应用，越来越多的基因被发现与DEE相关。这些发现将为临床工作中DEE致病基因的检测提供依据，同时将有助于加深对DEE发病机制的理解。本文主要对DEE的遗传学病因及诊疗的相关研究进展展开综述，以期帮助临床医生早期识别相关基因突变，从而加快疾病诊断并及时实施最佳治疗。

关键词: 基因变异, 发育性和癫痫性脑病, OMIM数据库

Abstract:

Developmental and epileptic encephalopathy (DEE) is a clinically and genetically heterogeneous group of age-dependent neurological disorders characterized by onset of refractory seizures in infancy or early childhood and affected individuals with delayed or regressive psychomotor development. With the development of next-generation sequencing technology, especially the application of whole-exome sequencing technology, more and more genes have been found to be associated with DEE.These discoveries provide a basis for the detection of pathogenic genes for DEE in clinical work, and also help to deepen our understanding of the pathogenesis of DEE. In this review, we provide a comprehensive review of the genetic etiology, diagnosis and treatment of DEE, in order to assist clinicians in early identification of relevant gene mutations, thereby expediting disease diagnosis and timely implementation of optimal treatment.

Key words: genetic variation, DEE, OMIM database

金良, 陈语婕, 陈勇军. 发育性和癫痫性脑病遗传学病因及诊疗的研究进展[J]. 遗传, 2023, 45(7): 553-567.

Liang Jin, Yujie Chen, Yongjun Chen. Advances in genetic etiology, diagnosis and treatment of developmental and epileptic encephalopathy[J]. Hereditas(Beijing), 2023, 45(7): 553-567.

图/表 4

图1

表1

图2

表2

DEE相关的癫痫综合征"

癫痫综合征	癫痫发作特点	发病时期	相关变异基因(例)	发育特点
早期肌阵挛性脑病 (early myoclonic encephalopathy，EME)	顽固性肌阵挛性癫痫发作和严重早期脑病	出生后前 2个月	ERBB4	可发展为小头畸形，严重的发育迟缓
大田原综合征 (Ohtahara syndrome，OS)	强直性癫痫发作占主导地位，肌阵挛性癫痫发作不常见	1~3个月	SCN2A、CDKL5、 SLC25A22	可发展为小头畸形，严重的发育迟缓
婴儿痉挛症(West syndrome，WS)	癫痫发作性痉挛	3~12个月	ARX、GRIN2B、SPTAN1、STXBP1	整体发育障碍(伴或不伴消退)通常见于癫痫发作时。偶尔发育可能是正常的
Dravet综合征(Dravet syndrome，DS)	大约60%的病例中，第一次癫痫发作与发烧有关	6个月左右	SCN1A	共济失调和锥体体征可能出现，发育可能消退
婴儿期癫痫伴有迁移性局灶性癫痫发作(epilepsy of infancy with migrating focal seizures，EIMFS)	出生后第一年出现难治性局灶性癫痫发作，伴有严重的脑病	出生后前 6个月	KCNT1、ATP7A、SCN2A	可发展为小头畸形，可发育延迟
非进展性疾病中的肌阵挛性脑病(myoclonic encephalopathy in non- progressive disorders，MENPD)	反复发作的肌阵挛性癫痫持续状态	出生后前 5年	DHDDS	通常可见严重的神经和发育障碍
Lennox-Gastaut综合征(Lennox- Gastaut syndrome，LGS)	多种类型的难治性癫痫发作	1~7岁	CHD2	通常可见发育停滞或消退
癫痫性脑病伴睡眠期间持续性棘波(epileptic encephalopathy with continuous spike-and-wave during sleep，CSWS)	睡眠期间连续的尖波及癫痫发作	2~12岁	CDKL5	认知、行为和精神功能的进行性下降
Landau Kleffner综合征(Landau Kleffner syndrome，LKS)	癫痫发作可在预测的年龄自发缓解	2~8岁	GRIN2A	既往发育和认知正常的儿童中亚急性发作的获得性失语症

表2

参考文献 99

[1]	Engel J, International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia, 2001, 42(6): 796-803.
[2]	Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, Van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia, 2010, 51(4): 676-685.
[3]	Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521. doi: 10.1111/epi.13709 pmid: 28276062
[4]	Zhou P, He N, Zhang JW, Lin ZJ, Wang J, Yan LM, Meng H, Tang B, Li BM, Liu XR, Shi YW, Zhai QX, Yi YH, Liao WP. Novel mutations and phenotypes of epilepsy- associated genes in epileptic encephalopathies. Genes Brain Behav, 2018, 17(8): e12456. doi: 10.1111/gbb.2018.17.issue-8
[5]	Symonds JD, Mctague A. Epilepsy and developmental disorders: next generation sequencing in the clinic. Eur J Paediatr Neurol, 2020, 24: 15-23. doi: 10.1016/j.ejpn.2019.12.008
[6]	Kolc KL, Sadleir LG, Scheffer IE, Ivancevic A, Roberts R, Pham DH, Gecz J. A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity. Mol Psychiatry, 2019, 24(2): 241-251. doi: 10.1038/s41380-018-0066-9
[7]	Fuchs C, Rimondini R, Viggiano R, Trazzi S, De Franceschi M, Bartesaghi R, Ciani E. Inhibition of GSK3β rescues hippocampal development and learning in a mouse model of CDKL5 disorder. Neurobiol Dis, 2015, 82: 298-310. doi: S0969-9961(15)30003-6 pmid: 26143616
[8]	Tong P, Liu Y. Advances in genetics of developmental and epileptic encephalopathy. J Epilepsy, 2022, 8(4): 338-341. doi: 10.1016/0896-6974(95)00055-0
	童培, 刘艳. 发育性及癫痫性脑病的遗传学研究进展. 癫痫杂志, 2022, 8(4): 338-341. doi: 10.1016/0896-6974(95)00055-0
[9]	Zayat V, Szlendak R, Hoffman-Zacharska D. Concise review: stem cell models of SCN1A-related encephalopathies-current perspective and future therapies. Cells, 2022, 11(19): 3119. doi: 10.3390/cells11193119
[10]	Van Loo KMJ, Carvill GL, Becker AJ, Conboy K, Goldman AM, Kobow K, Lopes-Cendes I, Reid CA, Van Vliet EA, Henshall DC. Epigenetic genes and epilepsy - emerging mechanisms and clinical applications. Nat Rev Neurol, 2022, 18(9): 530-543. doi: 10.1038/s41582-022-00693-y
[11]	Scheffer IE, French J, Hirsch E, Jain S, Mathern GW, Moshé SL, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. Classification of the epilepsies: new concepts for discussion and debate-special report of the ILAE Classification Task Force of the Commission for Classification and Terminology. Epilepsia Open, 2016, 1(1-2): 37-44.
[12]	Shi JB, Wang DY, Xia Q, Gao X. The effects of m⁶A modification in central nervous system function and disease. Hereditas(Beijing), 2020, 42(12): 1156-1167.
	史佳宾, 王大勇, 夏晴, 高旭. m-6A修饰对中枢神经系统功能及疾病的影响. 遗传, 2020, 42(12): 1156-1167.
[13]	Cannon SC. Epilepsy channelopathies go neddy: stabilizing NaV1.1 channels by neddylation. J Clin Invest, 2021, 131(8): e148370. doi: 10.1172/JCI148370
[14]	Symonds JD, Zuberi SM, Stewart K, Mclellan A, O'regan M, Macleod S, Jollands A, Joss S, Kirkpatrick M, Brunklaus A, Pilz DT, Shetty J, Dorris L, Abu-Arafeh I, Andrew J, Brink P, Callaghan M, Cruden J, Diver LA, Findlay C, Gardiner S, Grattan R, Lang B, Macdonnell J, Mcknight J, Morrison CA, Nairn L, Slean MM, Stephen E, Webb A, Vincent A, Wilson M. Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort. Brain, 2019, 142(8): 2303-2318. doi: 10.1093/brain/awz195 pmid: 31302675
[15]	Hattori J, Ouchida M, Ono J, Miyake S, Maniwa S, Mimaki N, Ohtsuka Y, Ohmori I. A screening test for the prediction of Dravet syndrome before one year of age. Epilepsia, 2008, 49(4): 626-633. pmid: 18076640
[16]	Connolly MB. Dravet syndrome: diagnosis and long- term course. Can J Neurol Sci, 2016, 43 Suppl 3: S3-S8.
[17]	Dravet C. The core Dravet syndrome phenotype. Epilepsia, 2011, 52 Suppl 2: 3-9. doi: 10.1111/j.1528-1167.2011.02994.x pmid: 21463272
[18]	Kalume F. Sudden unexpected death in Dravet syndrome: respiratory and other physiological dysfunctions. Respir Physiol Neurobiol, 2013, 189(2): 324-328. doi: 10.1016/j.resp.2013.06.026 pmid: 23850567
[19]	Fujiwara T, Sugawara T, Mazaki-Miyazaki E, Takahashi Y, Fukushima K, Watanabe M, Hara K, Morikawa T, Yagi K, Yamakawa K, Inoue Y. Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures. Brain, 2003, 126(Pt 3): 531-546. pmid: 12566275
[20]	Depienne C, Trouillard O, Saint-Martin C, Gourfinkel-An I, Bouteiller D, Carpentier W, Keren B, Abert B, Gautier A, Baulac S, Arzimanoglou A, Cazeneuve C, Nabbout R, Leguern E. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet, 2009, 46(3): 183-191. doi: 10.1136/jmg.2008.062323 pmid: 18930999
[21]	Smuk V, López-Rivera JA, Leu C, Lal D. The phenotypic spectrum associated with loss-of-function variants in monogenic epilepsy genes in the general population. Eur J Hum Genet, 2023, 31(2): 243-247. doi: 10.1038/s41431-022-01211-w
[22]	Ogiwara I, Ito K, Sawaishi Y, Osaka H, Mazaki E, Inoue I, Montal M, Hashikawa T, Shike T, Fujiwara T, Inoue Y, Kaneda M, Yamakawa K. De novo mutations of voltage- gated sodium channel alphaII gene SCN2A in intractable epilepsies. Neurology, 2009, 73(13): 1046-1053. doi: 10.1212/WNL.0b013e3181b9cebc pmid: 19786696
[23]	Zhang JJ.Genetic and phenotypic characteristics of SCN8A-related epilepsy in Chinese children[Dissertation]. Chongqing Medical University, 2022.
	张俊娇.SCN8A基因变异相关癫痫的临床表型及遗传学特征研究[学位论文]. 重庆医科大学, 2022.
[24]	Zeng Q, Yang Y, Duan J, Niu XY, Chen Y, Wang D, Zhang J, Chen JY, Yang XL, Li JL, Yang ZX, Jiang YW, Liao JX, Zhang YH. SCN2A-related epilepsy: the phenotypic spectrum, treatment and prognosis. Front Mol Neurosci, 2022, 15: 809951. doi: 10.3389/fnmol.2022.809951
[25]	Wolff M, Brunklaus A, Zuberi SM. Phenotypic spectrum and genetics of SCN2A-related disorders, treatment options, and outcomes in epilepsy and beyond. Epilepsia, 2019, 60 Suppl 3: S59-S67.
[26]	Gardella E, Marini C, Trivisano M, Fitzgerald MP, Alber M, Howell KB, Darra F, Siliquini S, Bölsterli BK, Masnada S, Pichiecchio A, Johannesen KM, Jepsen B, Fontana E, Anibaldi G, Russo S, Cogliati F, Montomoli M, Specchio N, Rubboli G, Veggiotti P, Beniczky S, Wolff M, Helbig I, Vigevano F, Scheffer IE, Guerrini R, Møller RS. The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology, 2018, 91(12): e1112-e1124. doi: 10.1212/WNL.0000000000006199
[27]	Kim HJ, Yang DH, Kim SH, Kim B, Kim HD, Lee JS, Choi JR, Lee ST, Kang HC. The phenotype and treatment of SCN2A-related developmental and epileptic encephalopathy. Epileptic Disord, 2020, 22(5): 563-570. doi: 10.1684/epd.2020.1199
[28]	Wolff M, Johannesen KM, Hedrich UBS, Masnada S, Rubboli G, Gardella E, Lesca G, Ville D, Milh M, Villard L, Afenjar A, Chantot-Bastaraud S, Mignot C, Lardennois C, Nava C, Schwarz N, Gérard M, Perrin L, Doummar D, Auvin S, Miranda MJ, Hempel M, Brilstra E, Knoers N, Verbeek N, Van Kempen M, Braun KP, Mancini G, Biskup S, Hörtnagel K, Döcker M, Bast T, Loddenkemper T, Wong-Kisiel L, Baumeister FM, Fazeli W, Striano P, Dilena R, Fontana E, Zara F, Kurlemann G, Klepper J, Thoene JG, Arndt DH, Deconinck N, Schmitt-Mechelke T, Maier O, Muhle H, Wical B, Finetti C, Brückner R, Pietz J, Golla G, Jillella D, Linnet KM, Charles P, Moog U, Õiglane-Shlik E, Mantovani JF, Park K, Deprez M, Lederer D, Mary S, Scalais E, Selim L, Van Coster R, Lagae L, Nikanorova M, Hjalgrim H, Korenke GC, Trivisano M, Specchio N, Ceulemans B, Dorn T, Helbig KL, Hardies K, Stamberger H, De Jonghe P, Weckhuysen S, Lemke JR, Krägeloh-Mann I, Helbig I, Kluger G, Lerche H, Møller RS. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain, 2017, 140(5): 1316-1336. doi: 10.1093/brain/awx054 pmid: 28379373
[29]	Barker BS, Ottolini M, Wagnon JL, Hollander RM, Meisler MH, Patel MK. The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin. Epilepsia, 2016, 57(9): 1458-1466. doi: 10.1111/epi.13461 pmid: 27375106
[30]	Liu YY, Schubert J, Sonnenberg L, Helbig KL, Hoei-Hansen CE, Koko M, Rannap M, Lauxmann S, Huq M, Schneider MC, Johannesen KM, Kurlemann G, Gardella E, Becker F, Weber YG, Benda J, Møller RS, Lerche H. Neuronal mechanisms of mutations in SCN8A causing epilepsy or intellectual disability. Brain, 2019, 142(2): 376-390. doi: 10.1093/brain/awy326 pmid: 30615093
[31]	Atkin TA, Maher CM, Gerlach AC, Gay BC, Antonio BM, Santos SC, Padilla KM, Rader J, Krafte DS, Fox MA, Stewart GR, Petrovski S, Devinsky O, Might M, Petrou S, Goldstein DB. A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy. Epilepsia, 2018, 59(4): 802-813.
[32]	Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA. Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. J Biol Chem, 1998, 273(31): 19419-19423. doi: 10.1074/jbc.273.31.19419 pmid: 9677360
[33]	Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY. Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci USA, 2000, 97(9): 4914-4919. doi: 10.1073/pnas.090092797 pmid: 10781098
[34]	Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, Mckinnon D. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science, 1998, 282(5395): 1890-1893. doi: 10.1126/science.282.5395.1890 pmid: 9836639
[35]	Lim CX, Ricos MG, Dibbens LM, Heron SE. KCNT 1 mutations in seizure disorders: the phenotypic spectrum and functional effects. J Med Genet, 2016, 53(4): 217-225. doi: 10.1136/jmedgenet-2015-103508 pmid: 26740507
[36]	Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen HJ, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet, 2012, 44(11): 1255-1259. doi: 10.1038/ng.2441
[37]	Cherian C, Appendino JP, Ashtiani S, Federico P, Molnar CP, Kerr M, Khan A, Au PYB, Klein KM. The phenotypic spectrum of KCNT1: a new family with variable epilepsy syndromes including mild focal epilepsy. J Neurol, 2022, 269(4): 2162-2171. doi: 10.1007/s00415-021-10808-y
[38]	Benarroch EE. Neuronal voltage-gated calcium channels: brief overview of their function and clinical implications in neurology. Neurology, 2010, 74(16): 1310-1315. doi: 10.1212/WNL.0b013e3181da364b pmid: 20404312
[39]	Kordasiewicz HB, Thompson RM, Clark HB, Gomez CM. C-termini of P/Q-type Ca²⁺ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity. Hum Mol Genet, 2006, 15(10): 1587-1599. pmid: 16595610
[40]	Epi4K Consortium. De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am J Hum Genet, 2016, 99(2): 287-298. doi: 10.1016/j.ajhg.2016.06.003
[41]	Hommersom MP, Van Prooije TH, Pennings M, Schouten MI, Van Bokhoven H, Kamsteeg EJ, Van De Warrenburg BPC. The complexities of CACNA1A in clinical neurogenetics. J Neurol, 2022, 269(6): 3094-3108. doi: 10.1007/s00415-021-10897-9
[42]	Li XL, Li ZJ, Liang XY, Liu DT, Jiang M, Gao LD, Li H, Tang XQ, Shi YW, Li BM, He N, Li B, Bian WJ, Yi YH, Cheng CF, Wang J. CACNA1A mutations associated with epilepsies and their molecular sub-regional implications. Front Mol Neurosci, 2022, 15: 860662. doi: 10.3389/fnmol.2022.860662
[43]	Angelini C, Van Gils J, Bigourdan A, Jouk PS, Lacombe D, Menegon P, Moutton S, Riant F, Sole G, Tournier- Lasserve E, Trimouille A, Vincent M, Goizet C. Major intra-familial phenotypic heterogeneity and incomplete penetrance due to a CACNA1A pathogenic variant. Eur J Med Genet, 2019, 62(6): 103530. doi: 10.1016/j.ejmg.2018.08.011
[44]	Jiang X, Raju PK, D'avanzo N, Lachance M, Pepin J, Dubeau F, Mitchell WG, Bello-Espinosa LE, Pierson TM, Minassian BA, Lacaille JC, Rossignol E. Both gain-of- function and loss-of-function de novo CACNA1A mutations cause severe developmental epileptic encephalopathies in the spectrum of Lennox-Gastaut syndrome. Epilepsia, 2019, 60(9): 1881-1894. doi: 10.1111/epi.16316 pmid: 31468518
[45]	Rajakulendran S, Graves TD, Labrum RW, Kotzadimitriou D, Eunson L, Davis MB, Davies R, Wood NW, Kullmann DM, Hanna MG, Schorge S. Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy. J Physiol, 2010, 588(Pt 11): 1905-1913. doi: 10.1113/jphysiol.2009.186437
[46]	Pietrobon D. Insights into migraine mechanisms and CaV2.1 calcium channel function from mouse models of familial hemiplegic migraine. J Physiol, 2010, 588(Pt 11): 1871-1878. doi: 10.1113/jphysiol.2010.188003
[47]	Carvill GL, Weckhuysen S, Mcmahon JM, Hartmann C, Møller RS, Hjalgrim H, Cook J, Geraghty E, O'roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, Von Spiczak S, Nikanorova M, Hodgson BL, Gazina EV, Suls A, Shendure J, Dibbens LM, De Jonghe P, Helbig I, Berkovic SF, Scheffer IE, Mefford HC. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology, 2014, 82(14): 1245-1253. doi: 10.1212/WNL.0000000000000291 pmid: 24623842
[48]	Hamdan FF, Myers CT, Cossette P, Lemay P, Spiegelman D, Laporte AD, Nassif C, Diallo O, Monlong J, Cadieux-Dion M, Dobrzeniecka S, Meloche C, Retterer K, Cho MT, Rosenfeld JA, Bi WM, Massicotte C, Miguet M, Brunga L, Regan BM, Mo K, Tam C, Schneider A, Hollingsworth G, Deciphering Developmental Disorders Study, Fitzpatrick DR, Donaldson A, Canham N, Blair E, Kerr B, Fry AE, Thomas RH, Shelagh J, Hurst JA, Brittain H, Blyth M, Lebel RR, Gerkes EH, Davis-Keppen L, Stein Q, Chung WK, Dorison SJ, Benke PJ, Fassi E, Corsten-Janssen N, Kamsteeg EJ, Mau-Them FT, Bruel AL, Verloes A, Õunap K, Wojcik MH, Albert DVF, Venkateswaran S, Ware T, Jones D, Liu YC, Mohammad SS, Bizargity P, Bacino CA, Leuzzi V, Martinelli S, Dallapiccola B, Tartaglia M, Blumkin L, Wierenga KJ, Purcarin G, O'byrne JJ, Stockler S, Lehman A, Keren B, Nougues MC, Mignot C, Auvin S, Nava C, Hiatt SM, Bebin M, Shao YR, Scaglia F, Lalani SR, Frye RE, Jarjour IT, Jacques S, Boucher RM, Riou E, Srour M, Carmant L, Lortie A, Major P, Diadori P, Dubeau F, D'anjou G, Bourque G, Berkovic SF, Sadleir LG, Campeau PM, Kibar Z, Lafrenière RG, Girard SL, Mercimek-Mahmutoglu S, Boelman C, Rouleau GA, Scheffer IE, Mefford HC, Andrade DM, Rossignol E, Minassian BA, Michaud JL. High rate of recurrent de novo mutations in developmental and epileptic encephalopathies. Am J Hum Genet, 2017, 101(5): 664-685. doi: S0002-9297(17)30377-4 pmid: 29100083
[49]	Lim ET, Uddin M, De Rubeis S, Chan Y, Kamumbu AS, Zhang XC, D'gama AM, Kim SN, Hill RS, Goldberg AP, Poultney C, Minshew NJ, Kushima I, Aleksic B, Ozaki N, Parellada M, Arango C, Penzol MJ, Carracedo A, Kolevzon A, Hultman CM, Weiss LA, Fromer M, Chiocchetti AG, Freitag CM, Autism Sequencing Consortium, Church GM, Scherer SW, Buxbaum JD, Walsh CA. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Nat Neurosci, 2017, 20(9): 1217-1224.
[50]	Lemke JR, Hendrickx R, Geider K, Laube B, Schwake M, Harvey RJ, James VM, Pepler A, Steiner I, Hörtnagel K, Neidhardt J, Ruf S, Wolff M, Bartholdi D, Caraballo R, Platzer K, Suls A, De Jonghe P, Biskup S, Weckhuysen S. GRIN2B mutations in West syndrome and intellectual disability with focal epilepsy. Ann Neurol, 2014, 75(1): 147-154. doi: 10.1002/ana.24073 pmid: 24272827
[51]	Bleakley LE, Mckenzie CE, Soh MS, Forster IC, Pinares-Garcia P, Sedo A, Kathirvel A, Churilov L, Jancovski N, Maljevic S, Berkovic SF, Scheffer IE, Petrou S, Santoro B, Reid CA. Cation leak underlies neuronal excitability in an HCN1 developmental and epileptic encephalopathy. Brain, 2021, 144(7): 2060-2073. doi: 10.1093/brain/awab145 pmid: 33822003
[52]	Marini C, Porro A, Rastetter A, Dalle C, Rivolta I, Bauer D, Oegema R, Nava C, Parrini E, Mei D, Mercer C, Dhamija R, Chambers C, Coubes C, Thévenon J, Kuentz P, Julia S, Pasquier L, Dubourg C, Carré W, Rosati A, Melani F, Pisano T, Giardino M, Innes AM, Alembik Y, Scheidecker S, Santos M, Figueiroa S, Garrido C, Fusco C, Frattini D, Spagnoli C, Binda A, Granata T, Ragona F, Freri E, Franceschetti S, Canafoglia L, Castellotti B, Gellera C, Milanesi R, Mancardi MM, Clark DR, Kok F, Helbig KL, Ichikawa S, Sadler L, Neupauerová J, Laššuthova P, Šterbová K, Laridon A, Brilstra E, Koeleman B, Lemke JR, Zara F, Striano P, Soblet J, Smits G, Deconinck N, Barbuti A, Difrancesco D, Leguern E, Guerrini R, Santoro B, Hamacher K, Thiel G, Moroni A, Difrancesco JC, Depienne C. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain, 2018, 141(11): 3160-3178. doi: 10.1093/brain/awy263 pmid: 30351409
[53]	Toonen RFG, Wierda K, Sons MS, De Wit H, Cornelisse LN, Brussaard A, Plomp JJ, Verhage M. Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size. Proc Natl Acad Sci USA, 2006, 103(48): 18332-18337. doi: 10.1073/pnas.0608507103 pmid: 17110441
[54]	Han J, Pluhackova K, Böckmann RA. The multifaceted role of SNARE proteins in membrane fusion. Front Physiol, 2017, 8: 5. doi: 10.3389/fphys.2017.00005 pmid: 28163686
[55]	Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, Tohyama J, Uruno K, Kumada S, Nishiyama K, Nishimura A, Okada I, Yoshimura Y, Hirai SI, Kumada T, Hayasaka K, Fukuda A, Ogata K, Matsumoto N. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet, 2008, 40(6): 782-788. doi: 10.1038/ng.150
[56]	Abramov D, Guiberson NGL, Burré J. STXBP1 encephalopathies: clinical spectrum, disease mechanisms, and therapeutic strategies. J Neurochem, 2021, 157(2): 165-178. doi: 10.1111/jnc.v157.2
[57]	Ait-El-Mkadem S, Dayem-Quere M, Gusic M, Chaussenot A, Bannwarth S, François B, Genin EC, Fragaki K, Volker-Touw CLM, Vasnier C, Serre V, Van Gassen KLI, Lespinasse F, Richter S, Eisenhofer G, Rouzier C, Mochel F, De Saint-Martin A, Abi Warde MT, De Sain-Van Der Velde MGM, Jans JJM, Amiel J, Avsec Z, Mertes C, Haack TB, Strom T, Meitinger T, Bonnen PE, Taylor RW, Gagneur J, Van Hasselt PM, Rötig A, Delahodde A, Prokisch H, Fuchs SA, Paquis-Flucklinger V. Mutations in MDH2, encoding a krebs cycle enzyme, cause early-onset severe encephalopathy. Am J Hum Genet, 2017, 100(1): 151-159. doi: S0002-9297(16)30492-X pmid: 27989324
[58]	Koch J, Mayr JA, Alhaddad B, Rauscher C, Bierau J, Kovacs-Nagy R, Coene KLM, Bader I, Holzhacker M, Prokisch H, Venselaar H, Wevers RA, Distelmaier F, Polster T, Leiz S, Betzler C, Strom TM, Sperl W, Meitinger T, Wortmann SB, Haack TB. CAD mutations and uridine-responsive epileptic encephalopathy. Brain, 2017, 140(2): 279-286. doi: 10.1093/brain/aww300 pmid: 28007989
[59]	Lin C, Franco B, Rosner MR. CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. Hum Mol Genet, 2005, 14(24): 3775-3786. doi: 10.1093/hmg/ddi391 pmid: 16330482
[60]	Kalscheuer VM, Tao J, Donnelly A, Hollway G, Schwinger E, Kübart S, Menzel C, Hoeltzenbein M, Tommerup N, Eyre H, Harbord M, Haan E, Sutherland GR, Ropers HH, Gécz J. Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. Am J Hum Genet, 2003, 72(6): 1401-1411. doi: 10.1086/375538 pmid: 12736870
[61]	Archer HL, Evans J, Edwards S, Colley J, Newbury-Ecob R, O'callaghan F, Huyton M, O'regan M, Tolmie J, Sampson J, Clarke A, Osborne J. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet, 2006, 43(9): 729-734. doi: 10.1136/jmg.2006.041467 pmid: 16611748
[62]	Falk MJ, Li D, Gai XW, Mccormick E, Place E, Lasorsa FM, Otieno FG, Hou CP, Kim CE, Abdel-Magid N, Vazquez L, Mentch FD, Chiavacci R, Liang JL, Liu XZ, Jiang H, Giannuzzi G, Marsh ED, Yiran G, Tian LF, Palmieri F, Hakonarson H. AGC1 deficiency causes infantile epilepsy, abnormal myelination, and reduced N-acetylaspartate. JIMD Rep, 2014, 14: 77-85. doi: 10.1007/8904_2013_287 pmid: 24515575
[63]	Fassio A, Esposito A, Kato M, Saitsu H, Mei D, Marini C, Conti V, Nakashima M, Okamoto N, Olmez Turker A, Albuz B, Semerci Gündüz CN, Yanagihara K, Belmonte E, Maragliano L, Ramsey K, Balak C, Siniard A, Narayanan V, C4RCD Research Group, Ohba C, Shiina M, Ogata K, Matsumoto N, Benfenati F, Guerrini R. De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy. Brain, 2018, 141(6): 1703-1718.
[64]	Ng BG, Buckingham KJ, Raymond K, Kircher M, Turner EH, He M, Smith JD, Eroshkin A, Szybowska M, Losfeld ME, Chong JX, Kozenko M, Li CM, Patterson MC, Gilbert RD, Nickerson DA, Shendure J, Bamshad MJ, University of Washington Center for Mendelian Genomics, Freeze HH. Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation. Am J Hum Genet, 2013, 92(4): 632-636. doi: 10.1016/j.ajhg.2013.03.012 pmid: 23561849
[65]	Kodera H, Nakamura K, Osaka H, Maegaki Y, Haginoya K, Mizumoto S, Kato M, Okamoto N, Iai M, Kondo Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Hayasaka K, Sugahara K, Yuasa I, Wada Y, Matsumoto N, Saitsu H. De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy. Hum Mutat, 2013, 34(12): 1708-1714. doi: 10.1002/humu.22446
[66]	Kitamura K, Yanazawa M, Sugiyama N, Miura H, Iizuka- Kogo A, Kusaka M, Omichi K, Suzuki R, Kato-Fukui Y, Kamiirisa K, Matsuo M, Kamijo SI, Kasahara M, Yoshioka H, Ogata T, Fukuda T, Kondo I, Kato M, Dobyns WB, Yokoyama M, Morohashi KI. Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet, 2002, 32(3): 359-369. doi: 10.1038/ng1009 pmid: 12379852
[67]	Bienvenu T, Poirier K, Friocourt G, Bahi N, Beaumont D, Fauchereau F, Ben Jeema L, Zemni R, Vinet MC, Francis F, Couvert P, Gomot M, Moraine C, Van Bokhoven H, Kalscheuer V, Frints S, Gecz J, Ohzaki K, Chaabouni H, Fryns JP, Desportes V, Beldjord C, Chelly J. ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation. Hum Mol Genet, 2002, 11(8): 981-991. pmid: 11971879
[68]	Partington MW, Turner G, Boyle J, Gécz J. Three new families with X-linked mental retardation caused by the 428-451 dup(24bp) mutation in ARX. Clin Genet, 2004, 66(1): 39-45. pmid: 15200506
[69]	Proud VK, Levine C, Carpenter NJ. New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. Am J Med Genet, 1992, 43(1-2): 458-466. doi: 10.1002/(ISSN)1096-8628
[70]	Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M, Tohyama J, Akasaka N, Hayasaka K. A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression- burst pattern (Ohtahara syndrome). Am J Hum Genet, 2007, 81(2): 361-366. doi: 10.1086/518903
[71]	Kato M, Das S, Petras K, Kitamura K, Morohashi KI, Abuelo DN, Barr M, Bonneau D, Brady AF, Carpenter NJ, Cipero KL, Frisone F, Fukuda T, Guerrini R, Iida E, Itoh M, Lewanda AF, Nanba Y, Oka A, Proud VK, Saugier-Veber P, Schelley SL, Selicorni A, Shaner R, Silengo M, Stewart F, Sugiyama N, Toyama J, Toutain A, Vargas AL, Yanazawa M, Zackai EH, Dobyns WB. Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. Hum Mutat, 2004, 23(2): 147-159. doi: 10.1002/humu.10310 pmid: 14722918
[72]	Yang S, Yang LM, Liao HM, Fang HJ, Ning ZS, Liao CS, Wu LW. Genetic analysis of developmental and epileptic encephalopathy caused by novel biallelic SZT2 gene mutations in three Chinese Han infants: a case series and literature review. Neurol Sci, 2022, 43(8): 5039-5048. doi: 10.1007/s10072-022-06038-3
[73]	Levy AD, Omar MH, Koleske AJ. Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood. Front Neuroanat, 2014, 8: 116. doi: 10.3389/fnana.2014.00116 pmid: 25368556
[74]	Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell, 1996, 84(3): 345-357. doi: 10.1016/s0092-8674(00)81279-9 pmid: 8608588
[75]	Dibbens LM, Tarpey PS, Hynes K, Bayly MA, Scheffer IE, Smith R, Bomar J, Sutton E, Vandeleur L, Shoubridge C, Edkins S, Turner SJ, Stevens C, O'meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Jones D, Lee R, Madison M, Mironenko T, Varian J, West S, Widaa S, Wray P, Teague J, Dicks E, Butler A, Menzies A, Jenkinson A, Shepherd R, Gusella JF, Afawi Z, Mazarib A, Neufeld MY, Kivity S, Lev D, Lerman-Sagie T, Korczyn AD, Derry CP, Sutherland GR, Friend K, Shaw M, Corbett M, Kim HG, Geschwind DH, Thomas P, Haan E, Ryan S, Mckee S, Berkovic SF, Futreal PA, Stratton MR, Mulley JC, Gécz J. X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet, 2008, 40(6): 776-781. doi: 10.1038/ng.149 pmid: 18469813
[76]	Depienne C, Leguern E. PCDH19-related infantile epileptic encephalopathy: an unusual X-linked inheritance disorder. Hum Mutat, 2012, 33(4): 627-634. doi: 10.1002/humu.22029 pmid: 22267240
[77]	Gecz J, Thomas PQ. Disentangling the paradox of the PCDH19 clustering epilepsy, a disorder of cellular mosaics. Curr Opin Genet Dev, 2020, 65: 169-175. doi: S0959-437X(20)30112-X pmid: 32726744
[78]	Depienne C, Bouteiller D, Keren B, Cheuret E, Poirier K, Trouillard O, Benyahia B, Quelin C, Carpentier W, Julia S, Afenjar A, Gautier A, Rivier F, Meyer S, Berquin P, Hélias M, Py I, Rivera S, Bahi-Buisson N, Gourfinkel-An I, Cazeneuve C, Ruberg M, Brice A, Nabbout R, Leguern E. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet, 2009, 5(2): e1000381. doi: 10.1371/journal.pgen.1000381
[79]	Richards KL, Milligan CJ, Richardson RJ, Jancovski N, Grunnet M, Jacobson LH, Undheim EAB, Mobli M, Chow CY, Herzig V, Csoti A, Panyi G, Reid CA, King GF, Petrou S. Selective Na(V)1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proc Natl Acad Sci USA, 2018, 115(34): E8077-E8085.
[80]	Boerma RS, Braun KP, Van Den Broek MPH, Van Berkestijn FMC, Swinkels ME, Hagebeuk EO, Lindhout D, Van Kempen M, Boon M, Nicolai J, De Kovel CG, Brilstra EH, Koeleman BPC. Remarkable phenytoin sensitivity in 4 children with SCN8A-related epilepsy: a molecular neuropharmacological approach. Neurotherapeutics, 2016, 13(1): 192-197. doi: 10.1007/s13311-015-0372-8 pmid: 26252990
[81]	Shi S, Li JW, Sun FD, Chen YF, Pang CL, Geng YZ, Qi JL, Guo S, Wang XZ, Zhang HL, Zhan Y, An HL. Molecular mechanisms and structural basis of retigabine analogues in regulating KCNQ2 channel. J Membr Biol, 2020, 253(2): 167-181. doi: 10.1007/s00232-020-00113-6
[82]	Soldovieri MV, Freri E, Ambrosino P, Rivolta I, Mosca I, Binda A, Murano C, Ragona F, Canafoglia L, Vannicola C, Solazzi R, Granata T, Castellotti B, Messina G, Gellera C, Labalme A, Lesca G, Difrancesco JC, Taglialatela M. Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy. Pharmacol Res, 2020, 160: 105200. doi: 10.1016/j.phrs.2020.105200
[83]	Sands TT, Balestri M, Bellini G, Mulkey SB, Danhaive O, Bakken EH, Taglialatela M, Oldham MS, Vigevano F, Holmes GL, Cilio MR. Rapid and safe response to low-dose carbamazepine in neonatal epilepsy. Epilepsia, 2016, 57(12): 2019-2030. doi: 10.1111/epi.13596 pmid: 27888506
[84]	Hedrich UBS, Lauxmann S, Wolff M, Synofzik M, Bast T, Binelli A, Serratosa JM, Martínez-Ulloa P, Allen NM, King MD, Gorman KM, Zeev BB, Tzadok M, Wong-Kisiel L, Marjanovic D, Rubboli G, Sisodiya SM, Lutz F, Ashraf HP, Torge K, Yan P, Bosselmann C, Schwarz N, Fudali M, Lerche H. 4-Aminopyridine is a promising treatment option for patients with gain-of-function KCNA2- encephalopathy. Sci Transl Med, 2021, 13(609): eaaz4957. doi: 10.1126/scitranslmed.aaz4957
[85]	Milligan CJ, Li M, Gazina EV, Heron SE, Nair U, Trager C, Reid CA, Venkat A, Younkin DP, Dlugos DJ, Petrovski S, Goldstein DB, Dibbens LM, Scheffer IE, Berkovic SF, Petrou S. KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. Ann Neurol, 2014, 75(4): 581-590.
[86]	Fitzgerald MP, Fiannacca M, Smith DM, Gertler TS, Gunning B, Syrbe S, Verbeek N, Stamberger H, Weckhuysen S, Ceulemans B, Schoonjans AS, Rossi M, Demarquay G, Lesca G, Olofsson K, Koolen DA, Hornemann F, Baulac S, Rubboli G, Minks KQ, Lee B, Helbig I, Dlugos D, Møller RS, Bearden D. Treatment responsiveness in KCNT1-related epilepsy. Neurotherapeutics, 2019, 16(3): 848-857. doi: 10.1007/s13311-019-00739-y pmid: 31054119
[87]	De Nys R, Kumar R, Gecz J. Protocadherin 19 clustering epilepsy and neurosteroids: opportunities for intervention. Int J Mol Sci, 2021, 22(18): 9769. doi: 10.3390/ijms22189769
[88]	Trivisano M, Specchio N, Vigevano F. Extending the use of stiripentol to other epileptic syndromes: a case of PCDH19-related epilepsy. Eur J Paediatr Neurol, 2015, 19(2): 248-250. doi: 10.1016/j.ejpn.2014.11.008
[89]	Joshi C, Kolbe DL, Mansilla MA, Mason S, Smith RJH, Campbell CA. Ketogenic diet - A novel treatment for early epileptic encephalopathy due to PIGA deficiency. Brain Dev, 2016, 38(9): 848-851. doi: 10.1016/j.braindev.2016.04.004
[90]	Kwong AKY, Chu VLY, Rodenburg RJT, Smeitink J, Fung CW. ARX-associated infantile epileptic-dyskinetic encephalopathy with responsiveness to valproate for controlling seizures and reduced activity of muscle mitochondrial complex IV. Brain Dev, 2019, 41(10): 883-887. doi: 10.1016/j.braindev.2019.07.003
[91]	Gao YN, Irvine EE, Eleftheriadou I, Naranjo CJ, Hearn-Yeates F, Bosch L, Glegola JA, Murdoch L, Czerniak A, Meloni I, Renieri A, Kinali M, Mazarakis ND. Gene replacement ameliorates deficits in mouse and human models of cyclin-dependent kinase-like 5 disorder. Brain, 2020, 143(3): 811-832. doi: 10.1093/brain/awaa028 pmid: 32125365
[92]	Devinsky O, King L, Schwartz D, Conway E, Price D. Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder. Epilepsia, 2021, 62(7): e98-e102. doi: 10.1111/epi.16923 pmid: 33979451
[93]	Loi M, Gennaccaro L, Fuchs C, Trazzi S, Medici G, Galvani G, Mottolese N, Tassinari M, Giorgini RR, Milelli A, Ciani E. Treatment with a GSK-3β/HDAC dual inhibitor restores neuronal survival and maturation in an in vitro and in vivo model of CDKL5 deficiency disorder. Int J Mol Sci, 2021, 22(11): 5950. doi: 10.3390/ijms22115950
[94]	Gennaccaro L, Fuchs C, Loi M, Roncacè V, Trazzi S, Ait-Bali Y, Galvani G, Berardi AC, Medici G, Tassinari M, Ren E, Rimondini R, Giustetto M, Aicardi G, Ciani E. A GABA(B) receptor antagonist rescues functional and structural impairments in the perirhinal cortex of a mouse model of CDKL5 deficiency disorder. Neurobiol Dis, 2021, 153: 105304. doi: 10.1016/j.nbd.2021.105304
[95]	Wang J, Qiao JD, Liu XR, Liu DT, Chen YH, Wu Y, Sun Y, Yu J, Ren RN, Mei Z, Liu YX, Shi YW, Jiang M, Lin SM, He N, Li B, Bian WJ, Li BM, Yi YH, Su T, Liu HK, Gu WY, Liao WP. UNC13B variants associated with partial epilepsy with favourable outcome. Brain, 2021, 144(10): 3050-3060. doi: 10.1093/brain/awab164
[96]	Liu XR, Ye TT, Zhang WJ, Guo X, Wang J, Huang SP, Xie LS, Song XW, Deng WW, Li BM, He N, Wu QY, Zhuang MZ, Xu M, Shi YW, Su T, Yi YH, Liao WP, China Epilepsy Gene 1.0 Project. CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia. CNS Neurosci Ther, 2021, 27(10): 1146-1156. doi: 10.1111/cns.13692
[97]	Ma MG, Liu XR, Wu Y, Wang J, Li BM, Shi YW, Su T, Li B, Liu DT, Yi YH, Liao WP. RYR2 mutations are associated with benign epilepsy of childhood with centrotemporal spikes with or without arrhythmia. Front Neurosci, 2021, 15: 629610. doi: 10.3389/fnins.2021.629610
[98]	Tian Y, Zhai QX, Li XJ, Shi Z, Cheng CF, Fan CX, Tang B, Zhang Y, He YY, Li WB, Luo S, Hou C, Chen WX, Liao WP, Wang J. ATP6V0C is associated with febrile seizures and epilepsy with febrile seizures plus. Front Mol Neurosci, 2022, 15: 889534. doi: 10.3389/fnmol.2022.889534
[99]	Chen Z, Luo S, Liu ZG, Deng YC, He SL, Liu XR, Yi YH, Wang J, Gao LD, Li BM, Wu ZJ, Ye ZL, Liang DH, Bian WJ, Liao WP, China Epilepsy Gene 1.0 Project. CELSR1 variants are associated with partial epilepsy of childhood. Am J Med Genet B Neuropsychiatr Genet, 2022, 189(7-8): 247-56. doi: 10.1002/ajmg.b.v189.7-8

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编码的蛋白功能	功能亚分类	发育性和癫痫性脑病基因(OMIM收录)
离子通道	电压门控钠通道	SCN1A、SCN1B、SCN2A、SCN3A、SCN8A
	电压门控钾通道	KCNA2、KCNB1、KCNC2、KCNQ2、KCNT1、KCNT2
	电压门控钙通道	CACNA1A、CACNA1E、CACNA2
	配体门控离子通道GABA受体	GABRA1、GABRA2、GABRA5、GABRB1、GABRB2、GABRB3、GABRG2、GABBR2
	配体门控离子通道谷氨酸受体	FRRS1L、GRIN1、GRIN2B、GRIN2D
	HCN通道	HCN1
膜运输调节		STX1B、STXBP1、CPLX1、NSF、SLC1A2、AP3B2、NAPB
酶/酶调节剂	蛋白质/氨基酸代谢酶	ALG13、CDKL5、PIGA、PIGB、PIGP、PIGQ、SIK1、ST3GAL3、SYNJ1、PIGS、FBXO28、GLS、UFSP2、PARS2
	核酸代谢酶	PNKP、AARS1、ITPA、CAD、CHD2
	能量代谢酶	MDH2、GOT2、MDH1
	信号转导酶	PLCB1、GNAO1、RHOBTB2
	酶调节剂	PHACTR1、ARHGEF9、TBC1D24、DOCK7、CYFIP2
	其他	ADAM22、PPP3CA、UGP2、UGDH、GAD1、DNM1、CDK19、UBA5
转运蛋白	氨基酸转运蛋白	SLC25A22、SLC25A12、SLC38A3
	阴/阳离子转运蛋白	SLC13A5、SLC12A5、ATP6V1A、ATP1A2、ATP1A3、ATP6V0A1
	核苷酸-糖转运蛋白	SLC35A2
细胞骨架蛋白		SPTAN1、ACTL6B
细胞代谢及信号转导		ARX、WWOX、FGF12、FGF13、DMXL2、SZT2、NTRK2、YWHAG
细胞粘附分子		PCDH19
核酸结合蛋白		CUX2、NEUROD2、GUF1、HNRNPU、SMC1A、CELF2、EEF1A2
分子伴侣		CNPY3
不明确		NECAP1、DENND5A、PACS2、TRAK1、RNF13、DALRD3、HID1、MAST3、FZR1

发育性和癫痫性脑病遗传学病因及诊疗的研究进展

Advances in genetic etiology, diagnosis and treatment of developmental and epileptic encephalopathy

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