dravet综合征患者scn1a基因突变c.1738ct和c.37051gt体外剪接分析word格式论文.docxVIP

SCN1A mutations( c.1738CT and c.3705+1GT) in patients with Dravet syndrome:an in vitro splicing assaypostgraduate： Xia yong ren supervisor： Prof. Liao wei pingAbstractObjectiveAccording to the SCN1A mutations which were discovered in our laboratory，we predict the effects of mutations on splicing signals by bioinformatics and construct mini-gene and analyse pre-mRNA splicing in vitro。MethodsWe screened SCN1A mutations in Dravet syndrome patients which were confirmed in our hospital。If mutations were found at or near intron/exon splice sites， we analyse these mutations by bioinformatics 。If bioinformatics indicate that mutation have impact on splicing，mini-gene was constructed and analysed the splicing mutation in vitro。ResultsSCN1Amutation c.1738CT do not have impact on splicing，SCN1Amutation c.3705+1 G T mutations result in two abnormal transcripts, an intron 18 retent 20bp, an exon 18 delete 49bp。ConclusionSCN1A mutation c.1738CT do not have impact on splicing，SCN1A mutationc.1738C T is a nonsense mutation which lead to early termination of protein translation, the nonsense mutation may the reason of the diseaseSCN1Amutation c.3705+1GT may have impact on splicing which lead to Dravet syndrome.Key words: Dravet syndrome, SCN1A, splicing.前 言癫痫（Epilepsy）是一种非常常见的神经科疾患，年发病率在 4‰到 7‰之间， 是神经元异常放电导致的一过性的脑功能异常综合征，总体上具有短暂发作性和 重复刻板性特点，是发作性意识丧失的常见原因，不同类型的癫痫发作具有其相 应的特点。按照国际抗癫痫联盟的对癫痫综合征分类，有几种癫痫综合征属于癫 痫性脑病。癫痫性脑病(Epileptic encephalopathies)是癫痫领域的一大研究难点和热点， 常在婴儿或儿童期发病，患者一般具有多种类型的癫痫发作通常难以控制，脑电 图因综合征类型的不同而各具特点。严重的癫痫发作和持续性的癫痫样放电导致 患儿出现进行性加重的精神发育迟滞，主要表现为认知障碍和行为障碍，此为癫 痫性脑病区别于其它普通癫痫综合征的显著特点。癫痫性脑病一般治疗困难预后 不佳[1]。临床上常见的有婴儿痉挛症和 Lennox-Gastaut 综合征（Lennox-Gastaut Syndrome，LGS），此类癫痫性脑病一般可见明确病因如产伤和皮质发育不良等。 Dravet 综合征（Dravet syndrome，DS）也是一种癫痫性脑病，与上述癫痫综合 征明显不同的是该病一般不容易找到明确病因，早期患儿磁共振检查通常正常， 同时一般生化检查也无异常，常与热性惊厥（Febrile seizure，FS)关系密切。DS 又称婴儿重症肌阵挛癫痫（Severe myoclonic epilepsy of infancy，SMEI）， 由 Dravet 于 1978 年首先报道。临床上主要有如下特征，多在 1 岁以内起病，起 病前发育正常。疾病早期多为与发热相关的癫痫发作，相当一部分患者由低热或 热水浴引起，通常表现为复杂性热性惊厥，也就是发