癫痫型脑病的基因研究进展_Journal of Epilepsy

Authors：

李柯麓 ,  任惠

昆明医科大学第一附属医院干疗神经内科（昆明 650000）;

Corresponding author：

任惠, Email: likelu1994@126.com

Keywords：

癫痫型脑病; 基因; 突变

DOI：

10.7507/2096-0247.20180024

Video：

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癫痫型脑病（Epileptic encephalopathies，EEs）是癫痫异常导致进展性脑部功能障碍，是一种儿童期常见的脑部疾病，以多种严重的癫痫症候群为特征的神经系统功能紊乱性疾病，癫痫反复发作可导致慢性神经功能减退，几乎 100%EEs 患儿存在有认知障碍，50% 患儿智力极其低下，生命早期肌阵挛和不典型失神发作对认知影响较大。EEs 多在婴儿期发病，随着年龄的增长、日间发作和肌阵挛频率逐渐减少，但是高热、感染刺激下诱发可持续存在，因此青少年时期仍可发生热性惊厥持续状态。随着遗传生物学和遗传诊断技术的不断发展，对 EEs 的认识更加全面，二代测序技术的应用对婴儿时期 EEs 患儿基因检测有了新的突破，基因突变被认为是导致 EEs 的主要原因，EEs 的基因研究成了医学界关注的焦点，目前已发现导致 EEs 的癫痫基因达数十种，文章翻阅和整理了大量国内外相关文献，对 EEs 的癫痫基因进行总结，以期对临床治疗 EEs 提供依据和指导。

Citation： 李柯麓, 任惠. 癫痫型脑病的基因研究进展. Journal of Epilepsy, 2018, 4(2): 117-120. doi: 10.7507/2096-0247.20180024 Copy

1.	Sillanpää M, Lastunen S, Helenius H, et al. Regional differences and secular trends in the incidence of epilepsy in Finland: a nationwide 23-year registry study. Epilepsia, 2011, 52 (10): 1857-1867.
2.	Donner EJ, Camfield P, Brooks L, et al. Understanding death in children with epilepsy. Pediatr Neurol, 2017, 70: 7-15.
3.	Gerald B, Ramsey K, Belnap N, et al. Neonatal epileptic encephalopathy caused by de novo GNAO1 mutation misdiagnosed as atypical Rett syndrome: Cautions in interpretation of genomic test results. Semin Pediatr Neurol, 2017. [Available online].
4.	Thomas RH, Berkovic SF. The hidden genetics of epilepsyaclinically important new paradigm. Nat Rev Neurol, 2014, 10(5): 283-292.
5.	Martin HC, Kim GE, Pagnamenta AT, et al. Clinical whole-genome sequencing in severe early- onset epilepsy reveals newgenes and improves molecular diagnosis. Hum Mol Genet, 2014, 23(12): 3200-3211.
6.	Milh M, Cacciaqli P, Ravix C et al. Severe neonatal seizures: From molecular diagnosis to precision therapy?. Rev Neurol(Paris), 2016, 172(3): 171-173.
7.	Gerber SH, Rah JC, Min SW, et al. Conformational switch of syntaxin-1 controls synaptic vesiclefusion. Science, 2008, 321: 1507-1510.
8.	Milh M, Villeneuve N, Chouchane M, et al. Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. Epilepsia, 2011, 52(10): 1828-1834.
9.	Saitsu H, Kato M, Mizuguchi T, et al. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet, 2008, 40(6): 782-788.
10.	Saitsu H, Kato M, Okada I, et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia, 2010, 51(12): 2397-2405.
11.	Deprez L, Weckhuysen S, Holmgren P et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology, 2010, 75(13): 1159-1165.
12.	Bahi-Buisson N, Nectoux J, Rosas-Vargas H, et al. Key clinical features to identify girls with CDKL5 mutations. Brain, 2008, 131(Pt 10): 2647-2661.
13.	Nemos C, Lambert L, Giuliano F, et al. Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of french patients and review of the literature. ClinGenet, 2009, 76(4): 357-371.
14.	Melani F, Mei D, Pisano T, et al. CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life. DevMedChild Neurol, 2011, 53(4): 354-360.
15.	Liang JS, Shimojima K, Takayama R, et al. CDKL5 alterations lead to early epileptic encephalopathy in both genders. Epilepsia, 2011, 52 (10): 1835-1842.
16.	Campbell IM, Yatsenko SA, Hixson P, et al. Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A. GenetMed, 2012, 14(10): 868-876.
17.	Saitsu H, Tohyama J, Kumada T, et al. Dominant-negative mutations in alpha-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay. Am J Hum Genet, 2010, 86: 881-891.
18.	Okazaki S, Ohsawa M, Kuki I, et al. Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of x-linked lissencephaly with abnormal genitalia (XLAG). Acta Neuropathol, 2008, 116 (4): 453-462.
19.	Pavone P, Spalice A, Polizzi A, et al. Ohtahara syndrome with emphasis on recent genetic discovery. Brain Dev, 2012, 34(6): 459-468.
20.	Depienne C, Bouteiller D, Keren B, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles dravet syndrome but mainly affects females. PLoS Genet, 2009, 5(2): e1000381.
21.	Weckhuysen S, Mandelstam S, Suls A, et al. KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol, 2012, 71 (1): 15-25.
22.	Harkin LA, McMahon JM, Iona X, et al. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain, 2007, 130(Pt 3): 843-852.
23.	Usluer S, Salar S, Arslan M, et al. SCN1A gene sequencing in 46 Turkish epilepsy patients disclosed 12 novel mutations. Seizure, 2016, 39: 34-43.
24.	田小娟, 张月华, 杨小玲, 等. 547 例 Dravet 综合征患儿 SCN1A 基因突变与遗传特点研究. 癫痫杂志, 2016, 2(1): 3-8.
25.	Mefford HC, Yendle SC, Hsu C, et al. Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol, 2011, 70 (6): 974-985.
26.	Joshi C, Kolbe DL, Mansilla MA, et al. Reducing the cost of the diagnostic odyssey in early onset epileptic encephalopathies. Biomed Res, 2016, 2016: 6421039.
27.	Kim YO, Yang JH, Park C, et al. A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy. Brain Dev. 2016, 38 (8): 750-754.

1. Sillanpää M, Lastunen S, Helenius H, et al. Regional differences and secular trends in the incidence of epilepsy in Finland: a nationwide 23-year registry study. Epilepsia, 2011, 52 (10): 1857-1867.
2. Donner EJ, Camfield P, Brooks L, et al. Understanding death in children with epilepsy. Pediatr Neurol, 2017, 70: 7-15.
3. Gerald B, Ramsey K, Belnap N, et al. Neonatal epileptic encephalopathy caused by de novo GNAO1 mutation misdiagnosed as atypical Rett syndrome: Cautions in interpretation of genomic test results. Semin Pediatr Neurol, 2017. [Available online].
4. Thomas RH, Berkovic SF. The hidden genetics of epilepsyaclinically important new paradigm. Nat Rev Neurol, 2014, 10(5): 283-292.
5. Martin HC, Kim GE, Pagnamenta AT, et al. Clinical whole-genome sequencing in severe early- onset epilepsy reveals newgenes and improves molecular diagnosis. Hum Mol Genet, 2014, 23(12): 3200-3211.
6. Milh M, Cacciaqli P, Ravix C et al. Severe neonatal seizures: From molecular diagnosis to precision therapy?. Rev Neurol(Paris), 2016, 172(3): 171-173.
7. Gerber SH, Rah JC, Min SW, et al. Conformational switch of syntaxin-1 controls synaptic vesiclefusion. Science, 2008, 321: 1507-1510.
8. Milh M, Villeneuve N, Chouchane M, et al. Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. Epilepsia, 2011, 52(10): 1828-1834.
9. Saitsu H, Kato M, Mizuguchi T, et al. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet, 2008, 40(6): 782-788.
10. Saitsu H, Kato M, Okada I, et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia, 2010, 51(12): 2397-2405.
11. Deprez L, Weckhuysen S, Holmgren P et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology, 2010, 75(13): 1159-1165.
12. Bahi-Buisson N, Nectoux J, Rosas-Vargas H, et al. Key clinical features to identify girls with CDKL5 mutations. Brain, 2008, 131(Pt 10): 2647-2661.
13. Nemos C, Lambert L, Giuliano F, et al. Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of french patients and review of the literature. ClinGenet, 2009, 76(4): 357-371.
14. Melani F, Mei D, Pisano T, et al. CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life. DevMedChild Neurol, 2011, 53(4): 354-360.
15. Liang JS, Shimojima K, Takayama R, et al. CDKL5 alterations lead to early epileptic encephalopathy in both genders. Epilepsia, 2011, 52 (10): 1835-1842.
16. Campbell IM, Yatsenko SA, Hixson P, et al. Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A. GenetMed, 2012, 14(10): 868-876.
17. Saitsu H, Tohyama J, Kumada T, et al. Dominant-negative mutations in alpha-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay. Am J Hum Genet, 2010, 86: 881-891.
18. Okazaki S, Ohsawa M, Kuki I, et al. Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of x-linked lissencephaly with abnormal genitalia (XLAG). Acta Neuropathol, 2008, 116 (4): 453-462.
19. Pavone P, Spalice A, Polizzi A, et al. Ohtahara syndrome with emphasis on recent genetic discovery. Brain Dev, 2012, 34(6): 459-468.
20. Depienne C, Bouteiller D, Keren B, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles dravet syndrome but mainly affects females. PLoS Genet, 2009, 5(2): e1000381.
21. Weckhuysen S, Mandelstam S, Suls A, et al. KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol, 2012, 71 (1): 15-25.
22. Harkin LA, McMahon JM, Iona X, et al. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain, 2007, 130(Pt 3): 843-852.
23. Usluer S, Salar S, Arslan M, et al. SCN1A gene sequencing in 46 Turkish epilepsy patients disclosed 12 novel mutations. Seizure, 2016, 39: 34-43.
24. 田小娟, 张月华, 杨小玲, 等. 547 例 Dravet 综合征患儿 SCN1A 基因突变与遗传特点研究. 癫痫杂志, 2016, 2(1): 3-8.
25. Mefford HC, Yendle SC, Hsu C, et al. Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol, 2011, 70 (6): 974-985.
26. Joshi C, Kolbe DL, Mansilla MA, et al. Reducing the cost of the diagnostic odyssey in early onset epileptic encephalopathies. Biomed Res, 2016, 2016: 6421039.
27. Kim YO, Yang JH, Park C, et al. A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy. Brain Dev. 2016, 38 (8): 750-754.

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癫痫型脑病的基因研究进展

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