一种改良拷贝数变异检测技术在自然流产遗传学检测中的应用  

Application of a modi?ed copy number variation detection technique in spontaneous miscarriage heredity

作　　者：胡雯婧 陈勤芳[2] 吴怡[3] 韩旭[4] 郭晓奎 陶炯 HU Wenjing;CHEN Qinfang;WU Yi;HAN Xu;GUO Xiaokui;TAO Jiong(Department of Microbiology and Immunology,Shanghai Jiaotong University College of Basic Medical Sciences,Shanghai 200025,China;Family Planning Section,the International Peace Maternity and Child Health Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200030,China;Department of Prenatal Diagnostic Center,the International Peace Maternity and Child Health Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200030,China;Reproductive Genetics Laboratory,the International Peace Maternity and Child Health Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200030,China;Department of Prenatal Diagnostic Center,Shanghai General Hospital,Shanghai Jiaotong University,Shanghai 201620,China)

机构地区：[1]上海交通大学医学院基础医学院免疫学与微生物学系,上海200025 [2]上海交通大学医学院附属国际和平妇幼保健院计划生育科,上海200030 [3]上海交通大学医学院附属国际和平妇幼保健院产前诊断中心,上海200030 [4]上海交通大学医学院附属国际和平妇幼保健院生殖遗传科,上海200030 [5]上海交通大学附属第一人民医院产前诊断中心,上海201620

出　　处：《检验医学》2019年第7期637-642,共6页Laboratory Medicine

基　　金：申康第一轮促进市级医院临床技能与临床创新三年行动计划项目（16CR4019A)

摘　　要：目的探讨一种高通量多重基因拷贝数检测技术(CNVplex)在孕早期自然流产遗传学检测中的临床应用价值。方法收集196例孕早期自然流产组织,清除蜕膜后绒毛组织每份分为2个组,一组采用染色体核型分析技术检测,另一组提取DNA采用CNVplex进行检测,比较2种方法的检测结果。结果196例孕早期流产绒毛中,细胞培养成功175例(成功率为89.29%),染色体核型分析检出异常染色体核型98例(异常检出率为56%),包括染色体数目异常96例、结构异常2例;CNVplex检测成功194例(成功率为98.98%),检出拷贝数异常115例(异常检出率为59.29%),包括染色体整条拷贝数异常107例、染色体部分片段拷贝数异常8例。在染色体核型分析失败的21例样本中,CNVplex共检出染色体拷贝数异常16例。在175例2种方法都检测成功的样本中有10例结果不符,其中染色体核型分析检出的2例多倍体、2例嵌合体以及1例易位型22三体CNVplex未能检出;其余5例CNVplex结果显示为染色体部分片段拷贝数异常,而染色体核型结果为正常或不明确,该5例样本均采用随访夫妻染色体检测和荧光原位杂交(FISH)验证。结论CNVplex的检测成功率高,能有效检出染色体小片段拷贝数异常,适用于孕早期自然流产遗传学快速检测,是传统染色体核型分析技术的有益补充。Objective To investigate the role of a high-throughput multiplex gene copy number variation detection technique(CNVplex)in spontaneous miscarriage heredity during early pregnancy.Methods Chorionic villus samples from 196 cases of spontaneous miscarriage were collected and divided into 2 groups after removing the decidua.One group was detected by chromosome karyotype analysis,and the other group was detected by CNVplex.The results were compared and analyzed.Results Among the 196 cases of chorionic villus samples,chorionic villus was successfully cultured in 175 cases(89.29%),and abnormal karyotypes were detected in 98 cases(56%),including 96 cases of chromosome number abnormalities and 2 cases of structural abnormalities.A total of 194 cases were successfully detected by CNVplex(98.98%),and 115 cases of copy number abnormalities(59.29%),including 107 cases of aneuploidy and 8 cases of chromosome segment copy number abnormalities,were detected.Among the 21 cases failed in karyotype analysis,CNVplex detected 16 cases of chromosome copy number abnormalities.In the 175 cases that were analyzed successfully in both methods,10 cases showed inconsistency,and there were 2 cases of polyploidy,2 cases of chimera and 1 case of translocation trisomy 22 recognized by karyotype analysis,while it was beyond the CNVplex detection scope.The other 5 cases of structure aberration identified by CNVplex were missed in karyotype analysis,and the results were then verified by parents'karyotype and fluorescence in situ hybridization(FISH).Conclusions CNVplex has high detection success rate,it can effectively detect the copy number variation of small chromosome segments and greatly facilitates classical cytogenetics in the rapid detection of spontaneous miscarriage heredity during early pregnancy.

关 键 词：自然流产 拷贝数变异 核型分析 

分 类 号：R446.1[医药卫生—诊断学]