通过外显子组测序对1例孤独症谱系障碍患者的致病基因分析  

Analysis of pathogenic genes in a patient with ASD by exome sequencing

作　　者：黄丽 李佳敏[1,2] 朱华 李桦[2] 李红霞[2] 许文明[3] 谢江[1,2] HUANG Li;LI Jia-min;ZHU Hua;LI Hua;LI Hong-xia;XU Wen-ming;XIE Jiang(Clinical Medical College,Southwest Medical University,Luzhou,Sichuan 646000,China;不详)

机构地区：[1]西南医科大学临床医学院,四川泸州646000 [2]成都市第三人民医院,四川成都610031 [3]四川大学华西第二医院,四川成都610041

出　　处：《现代预防医学》2020年第12期2242-2245,共4页Modern Preventive Medicine

基　　金：四川省科技厅科研项目(2016JY0185);四川省卫生健康委员会科研课题(19PJ009)。

摘　　要：目的应用外显子测序技术对1例孤独症谱系障碍的男童进行外显子组测序分析,寻找致病基因。方法选择1例就读于自闭症特殊学校的5岁男童,收集其临床资料,提取外周静脉血DNA,应用Nimblegen外显子序列捕获芯片及高通量测序技术对外显子区域进行测序。结果通过全外显子组捕获测序发现了非同义突变11309个,移码突变365个,同义突变23075个,其中发现有4个基因的突变已有文献报道可能与孤独症谱系障碍的发病有关,这4个基因包括PTEN、AFF2、LAMB1、NRCAM。结论应用外显子组捕获测序对该例孤独症谱系障碍的男童进行测序分析显示,大量单核苷酸多态性可能与该病的发生有关,也进一步证实了PTEN、AFF2、LAMB1、NRCAM这4个基因可能与孤独症谱系障碍的发生有关,有待进一步大样本研究及实验室研究验证其在孤独症谱系障碍发病中的具体机制。Objective In this study,exome sequencing was used to analyze the exome of a boy with autism spectrum disorders(ASD).Methods A 5-year-old boy enrolled in a special school for autism(Wenjiang Beidou special kindergarden)was selected to collect clinical data,extract peripheral blood DNA,and sequence the exome region by Nimblegen exon sequence capture chip combined with high-throughput sequencing technology.Results Through capture sequencing,we found 11309 nonsynonymous mutations,365 frameshift mutations and 23075 synonymous mutations,among which 4 non-synonymous mutations genes,including PTEN,AFF2,LAMB1 and NRCAM,were reported to have association with the onset of ASD.Conclusion Performing sequencing analysis on a case of boy with autism spectrum disorders using exome sequencing,we find that there are large number of single nucleotide polymorphisms related to the occurrence of ASD possibly.Moreover,we further confirm that PTEN,AFF2,LAMB1 and NRCAM may be associated with the occurrence of autism spectrum disorders,and further large-sample study and laboratory study are needed to verify the specific mechanisms in the pathogenesis of autism spectrum disorders.

关 键 词：孤独症谱系障碍 全外显子组捕获测序 基因突变 

分 类 号：R34[医药卫生—基础医学]