16p11.2微缺失相关儿童癫痫的临床表型与遗传学特征分析

doi:10.7499/j.issn.1008-8830.2111110

摘要
图/表
参考文献(22)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (514 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的探究16p11.2微缺失相关儿童癫痫的临床表型与遗传学特征。方法回顾性收集200例应用全外显子测序技术进行癫痫遗传学分析的癫痫患儿，其中9例癫痫患儿为16p11.2微缺失，分析9例16p11.2微缺失患儿的临床表型及遗传学特征。结果 16p11.2微缺失检出率为4.5%（9/200）。9例患儿为3~10月龄的婴儿；癫痫发作形式为局灶运动性发作伴意识障碍，部分进展为全身强直-阵挛发作；发作间期脑电图为局灶或多灶性痫样放电，对抗癫痫药物反应良好。9例患儿16p11.2缺失片段大小在398~906 kb之间，缺失基因数为23~33个，且均为致病性变异，其中2例为母源性来源，1例为父源性来源，余均为新发变异。结论 16p11.2微缺失在癫痫患儿中有一定的检出率，16p11.2微缺失多为新发变异，且为基因大片段缺失；16p11.2微缺失相关儿童癫痫多在出生1年内起病且为药物反应性癫痫。引用格式：中国当代儿科杂志，2022，24（5）：585-590

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	赖重媛
	陈瑞华
	钟春兰
	吉明明
	李兵飞

关键词 ：癫痫, 16p11.2微缺失, 全外显子测序技术, 儿童

Abstract：Objective To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children. Methods The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed. Results The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children. Conclusions 16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.

Key words： Epilepsy 16p11.2 microdeletion Whole exon sequencing technology Child

收稿日期: 2021-11-19

通讯作者: 陈瑞华，男，副主任医师。Email：crh16899@sina.cn。 E-mail: crh16899@sina.cn

作者简介: 赖重媛，女，硕士研究生，主治医；

引用本文:

赖重媛,陈瑞华,钟春兰等. 16p11.2微缺失相关儿童癫痫的临床表型与遗传学特征分析[J]. 中国当代儿科杂志, 2022, 24(5): 585-590.

LAI Chong-Yuan,CHEN Rui-Hua,ZHONG Chun-Lan et al. Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children[J]. CJCP, 2022, 24(5): 585-590.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2111110 或 http://www.zgddek.com/CN/Y2022/V24/I5/585

	1 蒋萍, 张桐, 汤继宏, 等. 新生突变的16p11.2微缺失综合征(附1例报告及文献复习)[J]. 中国临床神经科学, 2021, 29(3): 303-309.
	Rein B, Yan Z. 16p11.2 copy number variations and neurodevelopmental disorders[J]. Trends Neurosci, 2020, 43(11): 886-901. PMID: 32993859. PMCID: PMC7606557. DOI: 10.1016/j.tins.2020.09.001.
	Matsuzaki J, Berman JI, Blaskey L, et al. Abnormal auditory mismatch fields in children and adolescents with 16p11.2 deletion and 16p11.2 duplication[J]. Biol Psychiatry Cogn Neurosci Neuroimaging, 2020, 5(10): 942-950. PMID: 32033921. DOI: 10.1016/j.bpsc.2019.11.005.
	Blackmon K, Thesen T, Green S, et al. Focal cortical anomalies and language impairment in 16p11.2 deletion and duplication syndrome[J]. Cereb Cortex, 2018, 28(7): 2422-2430. PMID: 28591836. DOI: 10.1093/cercor/bhx143.
	Bachmann-Gagescu R, Mefford HC, Cowan C, et al. Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity[J]. Genet Med, 2010, 12(10): 641-647. PMID: 20808231. DOI: 10.1097/GIM.0b013e3181ef4286.
	Vlaskamp DRM, Callenbach PMC, Rump P, et al. PRRT2-related phenotypes in patients with a 16p11.2 deletion[J]. Eur J Med Genet, 2019, 62(4): 265-269. PMID: 30125676. DOI: 10.1016/j.ejmg.2018.08.002.
	Kleinendorst L, van den Heuvel LM, Henneman L, et al. Who ever heard of 16p11.2 deletion syndrome? Parents' perspectives on a susceptibility copy number variation syndrome[J]. Eur J Hum Genet, 2020, 28(9): 1196-1204. PMID: 32415274. PMCID: PMC7608422. DOI: 10.1038/s41431-020-0644-6.
	Kleinendorst L, Sno M, van Haelst MM. A girl with 16p11.2 deletion syndrome[J]. Ned Tijdschr Geneeskd, 2019, 163: D3441. PMID: 30945833.
	Shinawi M, Liu P, Kang SH, et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size[J]. J Med Genet, 2010, 47(5): 332-341. PMID: 19914906. PMCID: PMC3158566. DOI: 10.1136/jmg.2009.073015.
	10 蔺朋武, 孟照琰, 冯暄, 等. 2例16p11.2微缺失综合征家系的临床表型及分子遗传学分析[J]. 兰州大学学报(医学版), 2021, 47(5): 81-85. DOI: 10.13885/j.issn.1000-2812.2021.05.014.
	11 葛婷, 崔云, 肖咏梅, 等. 16p11.2缺失综合征1例并文献复习[J]. 中国循证儿科杂志, 2014, 9(6): 452-455. DOI: 10.3969/j.issn.1673-5501.2014.06.010.
	Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology[J]. Epilepsia, 2017, 58(4): 512-521. PMID: 28276062. PMCID: PMC5386840. DOI: 10.1111/epi.13709.
	Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)[J]. Genet Med, 2020, 22(2): 245-257. PMID: 31690835. PMCID: PMC7313390. DOI: 10.1038/s41436-019-0686-8.
	Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology[J]. Epilepsia, 2017, 58(4): 522-530. PMID: 28276060. DOI: 10.1111/epi.13670.
	15 李小燕. 再发性16p11.2微缺失在不明原因智力低下/发育迟缓患儿中的患病率和表型异质性研究[D]. 南昌: 南昌大学, 2015.
	Zou D, Wang L, Liao J, et al. Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study[J]. Brain, 2021, 144(12): 3623-3634. PMID: 34145886. PMCID: PMC8719847. DOI: 10.1093/brain/awab233.
	Bassuk AG, Geraghty E, Wu S, et al. Deletions of 16p11.2 and 19p13.2 in a family with intellectual disability and generalized epilepsy[J]. Am J Med Genet A, 2013, 161A(7): 1722-1725. PMID: 23686817. PMCID: PMC4169108. DOI: 10.1002/ajmg.a.35946.
	Yang L, You C, Qiu S, et al. Novel and de novo point and large microdeletion mutation in PRRT2-related epilepsy[J]. Brain Behav, 2020, 10(5): e01597. PMID: 32237035. PMCID: PMC7218244. DOI: 10.1002/brb3.1597.
	Weber A, K?hler A, Hahn A, et al. Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome[J]. Neurogenetics, 2013, 14(3-4): 251-253. PMID: 24100940. DOI: 10.1007/s10048-013-0376-7.
	Calame DJ, Xiao J, Khan MM, et al. Presynaptic PRRT2 deficiency causes cerebellar dysfunction and paroxysmal kinesigenic dyskinesia[J]. Neuroscience, 2020, 448: 272-286. PMID: 32891704. DOI: 10.1016/j.neuroscience.2020.08.034.
	Chung WK, Roberts TP, Sherr EH, et al. 16p11.2 deletion syndrome[J]. Curr Opin Genet Dev, 2021, 68: 49-56. PMID: 33667823. DOI: 10.1016/j.gde.2021.01.011.
	Cooper GM, Coe BP, Girirajan S, et al. A copy number variation morbidity map of developmental delay[J]. Nat Genet, 2011, 43(9): 838-846. PMID: 21841781. PMCID: PMC3171215. DOI: 10.1038/ng.909.