不明原因智力障碍64例全基因组拷贝数变异分析  

Genome- wide copy number variations analysis in 64 patients with unexplained intellectual disability

作　　者：付春云[1] 范歆[1] 罗仕玉 苏家荪 沈亦平[1] 张月[1] 张淑杰[1] 胡旭昀 陈荣誉[1] 罗静思[1] 李川[1] 陈少科[1] 

机构地区：[1]广西壮族自治区妇幼保健院遗传代谢中心实验室,南宁530003

出　　处：《中华实用儿科临床杂志》2017年第12期924-927,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：上海市出生缺陷防治重点实验室开放课题（16DZKF1014）

摘　　要：目的分析智力障碍患儿的分子遗传基础，探讨单核苷酸多态性基因芯片（SNP—array）技术在该类型疾病检测中的应用价值。方法选择2013年1月至2015年6月广西壮族自治区妇幼保健院就诊的64例智力障碍患儿，提取其外周血DNA，采用Illumina Humancyto SNP-12300K基因芯片进行全基因组拷贝数变异（CNVs）检测，查询国际病理性CNV数据库（ClinVar、DECIPHER、OMIM等）、DGV（Database of Genomic Variants）数据库，检索PubMed数据库相关文献，对CNVs致病性进行分析。结果64例智力障碍患儿中16例检出CNVs，检出率为25％。其中，检出已知致病的微缺失／微重复综合征6例，明确致病的微缺失／微重复（非综合征）3例，染色体数目异常1例，非平衡易位1例，临床意义不明5例。16例CNVs中，6例微缺失／微重复片段〈5Mb，最小检出缺失片段0．53Mb，这在常规染色体核型分析中是无法检出的。结论SNP—array技术具有分辨率高、准确性好等优点，是智力障碍患儿遗传学诊断的有力工具。Objective To investigate the genetic basis of patients with intellectual disability,and to assess the application of single nucleotide polymorphisms （SNP） - array in the molecular diagnosis of intellectual disability. Methods Sixty -four patients with intellectual disability who were identified in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2013 to June of 2015 were enrolled. Genomic DNA was extracted from peripheral blood and was analyzed with Illumina Humancyto SNP - 12 300K gene array chip. All identified copy number variants （CNVs） were analyzed with references from databases such as ClinVar,DECIPHER,OM1M and DGV （ Database of Genomic Variants）, as well as comprehensive literature review from PubMed database to determine the pathogenicity of CNVs. Results Sixteen cases of the above 64 patients were found to have CNVs with genomic altera- tions,including 6 cases microdeletions/microduplications associated with known syndromes, 3 cases microdeletions and microduplications with clear clinical relevance （non -syndrome）, 1 case numerical chromosome aberration, 1 case unbalanced translocation and 5 cases CNVs of unknown clinical significance. The detection rate was 25% （16/64 cases）. Among these 16 abnormalities ,6 cases of them could not be detected by using karyotyping analysis because their sizes were less than 5 Mb, and the smallest detected missing fragment was 0.53 Mb. Conclusion SNP - array gene chip technique with the advantages of higher efficiency, high -resolution and good accuracy, which can be applied to the ge- netic diagnosis of intellectual disability.

关 键 词：智力障碍 微缺失/微重复 微阵列单核苷酸多态性 

分 类 号：R748[医药卫生—神经病学与精神病学]