两例Poirier-Bienvenu神经发育综合征患儿的临床及CSNK2B基因变异分析  

De novo variant of CSNK2B causes Poirier-Bienvenu neurodevelopmental syndrome: two case report

作　　者：张佳 李杨 罗欢 沈亚君 袁梦 杨作臻 甘靖 Zhang Jia;Li Yang;Luo Huan;Shen YaJun;Yuan Meng;Yang Zuozhen;Gan Jing(Department of Pediatrics,West China Second University Hospital,Sichuan University,Chengdu,Sichuan 610041,China;Key Laboratory of Obstetrics&Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education,Sichuan University,Chengdu,Sichuan 610041 China;Cipher Gene LLC,Beijing 100089,China)

机构地区：[1]四川大学华西第二医院儿科,出生缺陷与相关妇儿疾病教育部重点实验室 [2]发育与妇儿疾病四川省重点实验室,成都610041 [3]赛福解码(北京)基因科技有限公司,北京100089

出　　处：《中华医学遗传学杂志》2022年第5期484-487,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(82071686,81501301);四川省科技厅重点研发项目(2021YFS0093);四川大学华西第二医院科研基金(KL115,KL072)。

摘　　要：目的对2例Poirier-Bienvenu神经发育综合征患儿的临床特征及CSNK2B基因变异进行分析,明确其可能的致病原因,为临床诊断提供依据。方法选择四川大学华西第二医院确诊的2例Poirier-Bienvenu神经发育综合征患儿,分析临床表现、实验室检查、全外显子测序及拷贝数变异(CNV)测序分析,对候选的变异进行一代测序Sanger验证。结果2例患儿主要表现为癫痫,运动或智力发育落后;全外显子测序显示患儿1系CSNK2B基因c.291+4A>T杂合剪切突变,患儿2系CSNK2B拷贝数(CNV)缺失。患儿1未予特殊处理,随访8+月,癫痫发作及运动发育均好转;患儿2反复癫痫发作9+年,予左乙拉西坦及氯硝西泮抗癫痫治疗,现2年无癫痫发作,监测脑电图仍可见大量痫性放电,智力及语言发育稍落后。结论我们的研究进一步证明了CSNK2B致病变异与伴发育障碍的癫痫有关,丰富了CSNK2B基因变异谱。CSNK2B致病变异临床异质性较大,神经系统损伤严重程度差异大,预后不尽相同,且胼胝体发育不全可能是其临床表型之一。Objective To analyze the clinical characteristics and CSNK2B gene variant of 2 children with Poirier-Bienvenu neurodevelopmental syndrome,and to identify the possible pathogenic causes and provide evidence for clinical diagnosis.Methods Two children with Poirier-Bienvenu neurodevelopmental syndrome were selected from West China Second University Hospital,Sichuan University.The clinical manifestations,laboratory examination and CSNK2B gene variant were analyzed.Results The main manifestations of 2 children were epilepsy,motor or intellectual retardation.Whole exon sequencing showed that CSNK2B gene c.291+4A>T heterozygous splicing variant was found in case one,and CSNK2B copy number variation(CNV)was lost in case two.Case one received no special treatment,followed up for 8+months,seizures and motor development were improved;case two had recurrent seizures for 9+years,and received levetiracetam and clonazepam antiepileptic treatment.No seizures have occurred for 2 years now,and a large number of epileptic discharges can still be seen in video electroencephalogram(VEEG)with slightly backward intelligence and language development.Conclusion Our study further proves that the pathogenic variant of CSNK2B is related to epilepsy with developmental disorder,and enrich is the CSNK2B gene variant spectrum.The pathogenesis of CSNK2B has great clinical heterogeneity,with great difference in severity of nervous system injury and different prognosis,and agenesis of corpus callosum may be one of its clinical phenotypes.

关 键 词：癫痫 Poirier-Bienvenu神经发育综合征 CSNK2B基因 外显子测序 

分 类 号：R741[医药卫生—神经病学与精神病学]