Poirier-Bienvenu神经发育综合征遗传学分析  

Genetic analysis of Poirier-Bienvenu neurodevelopmental syndrome

作　　者：童文佳 宋从磊 许愿愿 李敏 金丹群 TONG Wenjia;SONG Conglei;XU Yuanyuan;LI Min;JIN Danqun(Department of Pediatric Intensive Care Unit,Anhui Provincial Children's Hospital,Hefei 230051,Anhui,China;Department of Neurology,Anhui Provincial Children's Hospital,Hefei 230051,Anhui,China)

机构地区：[1]安徽省儿童医院重症医学科,安徽合肥230051 [2]安徽省儿童医院神经内科,安徽合肥230051

出　　处：《检验医学》2023年第2期112-116,共5页Laboratory Medicine

基　　金：安徽医科大学校级科研基金(2019xkj081)。

摘　　要：目的采用全外显子组家系测序(Trio-WES)分析1例早发性癫痫患儿的基因变异情况,探讨Poirier-Bienvenu神经发育综合征(POBINDS)的致病因素。方法收集1例早发性癫痫患儿的临床资料,对该患儿及其父母行Trio-WES,变异位点采用Sanger测序进行验证。通过生物信息学分析评估变异位点的危害性。结果患儿于3月龄时即表现出反复肌阵挛性癫痫发作,行丙戊酸钠治疗后,虽发作频次有所降低,但仍无法控制。Trio-WES结果提示患儿CSNK2B基因发生错义变异[c.560T>G(p.Leu187Arg)],其父母该位点均为野生型,属新发变异。根据基因检测结果和临床症状,患儿被明确诊断为POBINDS。检索公共SNP数据库(ESP数据库、千人基因组数据库和ExAC数据库)未发现该变异位点信息。Sanger测序证实该变异位点存在。蛋白结构模拟分析结果显示,c.560T>G(p.Leu187Arg)变异可能会导致酪蛋白激酶2(CK2)四聚体结构稳定性降低,从而影响其生物学功能。结论CSNK2B基因变异导致的POBINDS可能是患儿癫痫反复发作的致病因素,提示临床对于早发性、难治性癫痫,应考虑POBINDS的可能。Objective To analyze the gene mutation of a child with early-onset seizures by trio-whole-exome sequencing(Trio-WES),and to investigate the pathogenic factors of Poirier-Bienvenu neurodevelopmental syndrome(POBINDS).Methods The clinical data of a child with early-onset seizures were collected,Trio-WES was performed on the child and his parents,and the mutation sites were verified by Sanger sequencing.The hazards of mutation sites were assessed by bioinformatics analysis.Results The child exhibited recurrent myoclonic seizures at the age of 3 months.Although the frequency of seizures was decreased after treatment with sodium valproate,it was still uncontrollable.Trio-WES results indicated that the child had a missense mutation[c.560T>G(p.Leu187Arg)]in CSNK2B gene.The mutation sites of his parents were wild-type,which was a de novo mutation site.According to the results of genetic analysis and clinical symptoms,the child was definitely diagnosed as POBINDS.A search of public SNP databases(ESP database,1000 Genomes database and ExAC database)did not find that the mutation site was included.Sanger sequencing confirmed the existence of mutation site.The results of protein structure simulation analysis showed that the c.560T>G(p.Leu187Arg)may lead to a decreasing in the stability of casein kinase 2(CK2)tetramer structure,thereby affecting its biological function.Conclusions POBINDS caused by CSNK2B gene mutation may be the pathogenic factor of recurrent myoclonic seizures in children,suggesting that the possibility of POBINDS should be considered in the clinical treatment of early-onset seizures.

关 键 词：CSNK2B基因 全外显子组家系测序 Poirier-Bienvenu神经发育综合征 早发性癫痫 

分 类 号：R446.1[医药卫生—诊断学]