癫痫失语疾病谱GRIN2A基因突变研究  

Study of GRIN2A mutations in epilepsy-aphasia spectrum disorders

作　　者：钱萍[1] 杨小玲[1] 许小菁 刘晓燕[1] 张月华[1] 杨志仙[1] Qian Ping;Yang Xiaoling;Xu Xiaojing;Liu Xiaoyan;Zhang Yuehua;Yang Zhixian(Department of Pediatrics, Peking University First Hospital, Beijing 100034, China;Department of Pediatrics, China-Japan Friendship Hospital, Beijing 100029, China)

机构地区：[1]北京大学第一医院儿科,100034 [2]中日友好医院儿科,北京100029

出　　处：《中华医学遗传学杂志》2018年第3期314-318,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨癫痫失语疾病谱（epilepsy—aphasia spectrum，EAS）患JLGRIN2A基因的突变率及临床遗传学特点。方法以Landau—Kleffner综合征（Landau-Kleffner syndrome，LKs）、癫痫伴慢波睡眠期持续棘慢波（epilepsy with continuous spikes and waves during slow sleep，CSWS）、儿童良性癫痫伴中央颞区棘波（benign childhood epilepsy with centrotemporal spikes，BECT）及BECT变异型患儿为研究对象，采用Sanger测序法筛查GRIN2A基因的突变，并分析EAS患儿的临床遗传学特点。结果共收集到122例EAS患儿，包括9例LKS、26例CSWS、42例BECT变异型及45例BECT。该组患儿癫痫发作或失语的平均起病年龄为5岁（10个月至11岁）。GRIN2A突变筛查在4例无血缘关系的患儿中分别发现了1个可能致病的错义突变，包括c．2278G〉A（p．G760S）、C．4153G〉T（P．D1385Y）、C．1364G〉A（p．C455Y）和C．691T〉C（p．C231R），其中1例为LKS，其余3例为BECT变异型。GRIN2A在LKS和BECT变异型中的突变率分别为11．1％（1／9）和7．2％（3／42），而在26例CSWS及45例BECT患儿则均未发现突变。在122例患儿中，25例（20．5％）有热性惊厥或癫痫阳性家族史，但均未携带GRIN2A突变。结论EAS患儿可携带GRIN2A基因突变，但突变率相对较低。GRIN2A突变阴性的患儿中家族史为阳性者占一定的比例，提示EAS可能具有复杂的遗传学机制。Objective To detect potential mutations of the glutamate receptor subunit （GRINgA） gene and delineate the clinical-genetic characteristics of patients with epilepsy-aphasia spectrum （EAS） disorders. Methods One hundred twenty two patients with Landau-Kleffner syndrome （LKS）, epileptic eneephalopathy with continuous spike-and-wave during sleep （CSWS）, benign childhood epilepsy with centrotemporal spikes （BECT） and BECT variants were recruited. Potential mutations of the GRINgA gene were screened with Sanger sequencing. And clinical-genetic characteristics for all patients were analyzed. Results The patients have included 9 LKS, 26 CSWS, 42 BECT variants and 45 BECT. The mean age of onset of seizure or aphasia was 5 years old （10 months to 11 years）. Mutation screening has detected 4 possible pathogenic missense mutations including c. 2278G〉A （p. G760S）, c. 4153G〉T （p. D1385Y）, c. 1364G〉A （p. C455Y） and c. 691T〉C （p. C231R） in four unrelated probands, which comprised one case with LKS and three with BECT variants. The mutation rate was 11.1% （1/9） for LKS and 7.2%（3/42） for BECT variants. No GRIN2A mutation was found in the 26 patients with CSWS and 45 patients with BECT. Among the 122 probands, 25 （20.5%） patients without a GRIN2A mutation had a positive family history of febrile seizures or epilepsy. Conclusion GRIN2A mutations do exist in EAS patients, but with a relatively low rate. A proportion of EAS patients without a GRIN2A mutation have a positive family history, which suggested a complex mechanism for EAS.

关 键 词：GRIN2A基因 癫痫失语疾病谱 癫痫伴慢波睡眠期持续棘慢波 Landau-Kleffner 综合征 儿童良性癫痫伴中央颞区棘波 

分 类 号：R742.1[医药卫生—神经病学与精神病学]