广西不同民族儿童孤独症的流行现况及遗传易感基因研究

The prevalence of autism has significantly increased over years. The confirmed etiology and effective treatment of autism have not been reported, while it not only affect the development of psychology and social adaptability of children, but also has become a heavy burden of family and society. Therefore, it is of great important and urgency to find out the etiology of autism to prevention and reduce the occurrence of autism. In this study, a cross-sectional study with stratified-cluster sampling method will be conducted firstly to screen all of sampling children of different nationalities to describe the status and epidemic feature of autism in 2-6 years old children in Guangxi Zhuang Autonomous Region, which can provide basic epidemiological data to expand the database of autism research of China. Then those confirmed autism cases will be included in a 1:2 matched case-control study to explore the association between autism and tagSNPs from five genes loci at GRM8(7q31.1-q32.1),MET(7q31),RELN(7q22),CNTNAP2(7q35),FOXP2(7q31) by using the Taqman probe technology.Gene-gene interaction will be examined by using General Linear Model and Combinatorial partitioning method.Then exon sequencing technology will be used to find out new mutation sites in all candicate genes that may cause autism. The distribution of susceptibility genes among nuclear family of children with autism will be detected. The results of the present research could lay the foundation for carrying on a larger scope of genetics research of autism in China in the future, and can provide evidence for making specific interventions to prevention and reduce the incidence of autism in Guangxi region.

儿童孤独症发病率呈上升趋势，但病因尚不明确，亦无有效的治疗方法，常伴随患儿终身，严重影响其社会适应能力，并给家庭和社会带来沉重的负担，因此明确孤独症的流行特征、找出病因从根本上预防孤独症的发生是孤独症研究的热点问题。本研究拟首先通过现况研究的方法分层整群抽样调查广西汉、壮、瑶、苗四个民族2-6岁儿童孤独症的流行现况及特征，确定孤独症病例，为扩大我国孤独症研究数据库提供客观的流行病学数据；其次，以上述调查为基础进行1:2配对病例对照研究分析孤独症热点易感区域7号染色体上GRM8、MET、RELN、CNTNAP2、FOXP2基因遗传变异与广西不同民族儿童孤独症发生的相关性，重点探讨基因-基因交互作用对疾病易感性的影响。再利用外显子捕获测序技术对目前报道过的所有孤独症候选易感基因的全部外显子进行序列分析，探索新的基因突变类型或新的致病基因。为开展广西地区孤独症的防控工作提供理论依据。

孤独症是广泛性发展障碍疾病中最为常见的一种疾病，给家庭和社会带来极大负担，已成为全球性的公共健康问题。明确孤独症的流行特征、找出病因从根本上预防孤独症的发生是目前孤独症研究的热点问题。本研究在2015年6月至2018年9月期间，以广西13个市县2-6岁的18023名幼儿园在读儿童为研究对象，开展了广西地区儿童孤独症流行现况研究，本次调查筛查阳性儿童322人，筛查阳性率是17.87‰。最后确诊ASD患儿73人，患病率是4.05‰。其中男孩64人，患病率5.94%，女孩9人，患病率为1.24%，男女比例为4.8:1，不同性别儿童ASD患病率差异有统计学意义。6-7岁组儿童ASD患病率最高，为6.02‰，2-岁最低，不同年龄段ASD患病率差异有统计学意义。城镇儿童ASD患病率为5.07‰，农村为2.64‰，差异有统计学意义。但不同民族2-6岁儿童ASD患病率差异无统计学意义。在这个基础上开展孤独症遗传基础研究，先后到广西南宁、玉林、柳州、钦州、梧州等多城市集中采集孤独症生物样本15次，累积694个患儿，684个家系。为每一个患儿做染色体核型分析，694个患儿中发现的有意义的核型改变有7例，发现有意义上的风险基因有ASXL3、FOXP1、SCN2A、SIN3A、TNPO3等，但是缺乏重复验证结果。孤独症是个复杂疾病，但是所发现的风险基因合并起来也只能够解释10-20%的患者，后期要进一步加强对现有研究结果的总结分析，开展更多其他因素与孤独症的发病相关性。