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目的总结临床诊治中的难治性或某些疑为遗传相关的癫痫患儿的临床特点,并对其进行二代高通量基因测序及一代验证,分析突变基因与癫痫之间的关系,了解患儿的遗传模式,寻找致病或可能致病的突变基因。方法对2014年9月-2016年12月期间在河南省人民医院儿科神经内科门诊确诊癫痫的95例患儿及其父母建立完整家系资料库,采用二代高通量基因测序方法对其进行了基因检测,依据患儿临床特征及基因型进行分析。结果难治性或疑为遗传相关的患儿年龄发病范围较小,临床发作特点多种多样,多数(47/95,49.5%)需要两种及以上药物治疗,治疗效果一般,控制27例(28.4%),有效20例(21.1%),显效32例(33.7%),无效12例(12.6%),失访4例(4.2%)。少数(18/95,18.9%)预后较差,合并有运动、智力发育落后检测基因型结果,明确致病的基因共16例(16.8%),可能致病的基因共21例(22.1%),不致病的基因共30例(31.6%),未检测到突变基因共28例(29.5%)结论发现CASK、BRAF两个新的致病基因,国内报道甚少,在一定意义上扩充了神经发育相关的癫痫基因和癫痫关联基因的数目;SCN1A基因突变所致Dravet综合征的患儿的临床特征更严重,包括起病更早、发作频繁、治疗效果差;有明确致病基因的患儿,多数需要两种及以上抗癫痫药物联合应用,治疗困难。
Objective To summarize the clinical features of refractory or some suspected genetic-related epilepsy in clinical diagnosis and treatment, and carry out the second-generation high-throughput gene sequencing and generation verification, analyze the relationship between the mutated gene and epilepsy, understand Children’s genetic patterns, looking for pathogenic or may be pathogenic mutations in the gene. Methods A total of 95 pediatric patients diagnosed with epilepsy and their parents in pediatric neurology outpatient department of Henan Provincial People’s Hospital from September 2014 to December 2016 were enrolled in this study to establish a complete pedigree database. The second generation high-throughput gene sequencing method was used Genetic testing, based on clinical features and genotypes in children were analyzed. The results of refractory or suspected genetic age children with a smaller incidence of clinical features of a variety of clinical and varied, the majority (47 / 95,49.5%) need two or more drugs, the treatment effect in general, control of 27 cases ( 28.4%), effective in 20 cases (21.1%), markedly effective in 32 cases (33.7%), ineffective in 12 cases (12.6%) and lost in 4 cases (4.2%). A small number (18/95, 18.9%) had poor prognosis, combined with motor and mental retardation. Genotypes of 16 patients (16.8%) were confirmed and 21 of them were pathogenic (22.1%). 30 cases (31.6%) were not pathogenic and 28 cases were not detected (29.5%). Conclusions Two novel genes of CASK and BRAF were reported in China, with few reports in China. In a certain sense, The number of epilepsy genes and epilepsy-associated genes involved in neurodevelopment; the clinical features of children with Dravet syndrome due to mutations in the SCN1A gene are more severe, including earlier onset, frequent seizures, poor response to treatment; Children, most need two or more antiepileptic drugs in combination, the treatment is difficult.