【作者】 周颖；

【导师】 唐北沙；

【作者基本信息】 中南大学 ， 临床医学， 2013， 硕士

【摘要】 背景：特发性全面性癫痫(idiopathic generalized epilepsies, IGE)是一类与遗传易感因素有关相关的癫痫综合征。典型的临床表现有：失神发作、肌阵挛发作以及全面性强直阵挛发作(generalized tonic-clonic, GTC),部分患者可有失张力发作和强直性发作。患者青少年时期发病,无性别差异。患者神经系统体格检查、智力检测及磁共振(magnetic resonance imaging, MRI)检查可为正常,脑电图(electroencephalogram, EEG)检查表现为广泛性放电而背景波正常。外显子组测序：利用序列捕获技术将全基因组外显子区域序列捕获并富集后,进行高通量测序的基因组分析方法。具有高通量、经济高效、可发现低频变异(<5%)等优势,成为目前孟德尔遗传病的首选研究手段。主要包括目标区域序列的富集、DNA测序、生物信息学统计3个步骤。目的：为了筛查一常染色体显性遗传的IGE家系致病基因。方法：我们应用外显子组测序方法对家系中3名患者进行高通量测序。过滤各种已知SNP(Single Nucleotide Polymorphisms,单核苷酸的多态性)数据库后得到家系中3名患者共有的序列变异15个,然后对这15个变异进行生物信息学分析,对收集到的该家系所有样本进行Sanger测序验证。结果：未发现序列变异与疾病表型共分离。结论：提示上述个变异可能为新发现的SNP。更多还原

【Abstract】 Background:Idiopathic generalized epilepsies are a group of idiopathic epilepsies, which are genetically determined. The typical clinical manifestations include absence, myoclonic, generalized tonic-clonic (GTC), and potentially atonic and tonic seizures. The age at onset of IGE is adolescence juvenile era, and there is no difference between girls and boys. Neurological examination, intelligence quotient testing, and magnetic resonance imaging (MRI) findings are usually normal. Patients of IGE have similar electroencephalogram (EEG) findings, namely generalized epileptiform abnormalities with no abnormal background slowing.Exome sequencing:using sequence captures technology to capture and sequencing after Target-enrichment strategies of the genome analysis method. With high efficiency, and can find the low-frequency variation (<5%), that become the mainly method of Mendelian genetic disease research. Three steps of the exome sequencing is sample preparation, Sequencing and data analysis.Objective:To screening the causative gene of an idiopathic generalized epilepsies pedigree. Methods:In this study, exome sequencing was performed to screen the causative gene for three patients of the IGE family. And Sanger sequencing was used to verify the results.Consequently, fifteen genes with similar sequence variations were found in the three patients.Results:However, the followed Sanger sequencing excluded those sequence variations as causative ones from the IGE family. Sequence variations were not co-segregated with the Phenotype.Conclusion:which indicating the sequence variations might be SNP.更多还原