特发性癫痫患者基因突变与临床特征分析  

Analysis of gene mutation and clinical characteristics in patients with idiopathic epilepsy

作　　者：孙慧超[1,2] 王朝东[2] 李铭玉 李丽萍[2] 赵筱玲[2] 王玉平[2] 叶静[2] 

机构地区：[1]中国藏学研究中心北京藏医院 [2]首都医科大学宣武医院神经内科,北京100053

出　　处：《中华医学杂志》2017年第31期2439-2442,共4页National Medical Journal of China

摘　　要：目的 探讨中国癫痫患者基因突变与临床表现的相关性.方法 收集2014年1月至2016年7月在首都医科大学宣武医院就诊的特发性癫痫患者23例,发病年龄8个月至31岁.利用二代测序技术,筛查与癫痫相关的基因突变,部分突变通过家系内连续两代患者的Sanger测序得以验证.比较不同基因突变的携带者在癫痫主要临床特点（家族史、性别、发病年龄、发作形式、并发症）方面的差异.结果 在23例患者中共检出与癫痫发病可能相关的突变基因38个,这些患者多为儿童及青年发病,发病形式以强直阵挛为主,多不伴有智力障碍,病程良性.致病基因以离子通道、酶类、特殊蛋白类基因为主.携带离子通道和特殊功能蛋白基因突变的患者在性别、发病年龄、发作形式、家族史等临床特征方面差异无统计学意义（均P〉0.05）,但强直-阵挛的患者中检出离子通道基因突变的比例（15/15）高于特殊功能蛋白基因突变携带者（16/20）（P=0.066）.结论 二代测序技术是检测各类癫痫患者基因突变的有效手段,可用于临床辅助病因诊断.强直-阵挛发作形式可能与离子通道基因突变存在关联性.Objective To explore the association between gene mutations and clinical characteristics in Chinese patients with epilepsy.Methods A total of twenty-three patients with idiopathic epilepsy admitted to the Xuanwu Hospital of Capital Medical University from January 2014 to July 2016 were included.The age at onset of epilepsy ranged from 8 months to 31 years.All patients were screened for mutations by next-generation of sequencing （NGS）, using a targeted capture panel of epilepsy and related seizures to screen forgene causative for or related to epilepsy.Some mutations were verified for inheritance by Sanger sequencing of two generations in the family.The differences in clinical characteristics among different mutation carriers were compared.Results A total of 38 mutations were identified in 23 patients.Most of the patients presented with tonic-clonic seizures, and most were not accompanied by mental retardation.Causative genes were dominated by those encoding ion channel, enzyme and proteins with special functions.Although mutation carriers for genes encoding ion channel proteins and those with special functions were not significantly different in age at onset, types of seizure, family history or complications（P〉0.05）,patients presenting with tonic-clonic seizures had higher frequency of mutations in genes encoding ion channel （15/15）than those encoding proteins with special function（16/20）（P=0.066）.Conclusions NGS is a useful technology in detecting mutations in patients with various types of epilepsy and aiding in etiological diagnosis of the disease.Tonic-clonic seizures may correlate with mutations in genes encoding ion channel.

关 键 词：癫痫 表型 基因型 

分 类 号：R742.1[医药卫生—神经病学与精神病学]