比较基因组杂交微阵列技术在高龄孕妇产前诊断胎儿染色体异常中的应用  

Application of Array-based Comparative Genomic Hybridization in the Prenatal Diagnosis of Fetal Chromosomal Aberration in Gravidas with Advanced Age

作　　者：胡睿 张竹 王嘉敏[1,2] 李勤琴 杨运源[1,2] 肖莉柯 朱红梅 李玲萍 张李李 刘珊玲[1,2] 王和 胡婷[1,2] HU Rui;ZHANG Zhu;WANG Jia-min;LI Qin-qin;YANG Yun-yuan;XIAO Li-ke;ZHU Hong-mei;LI Ling-ping;ZHANG Li-li;LIU Shan-ling;WANG He;HU Ting(Department of Obstetrics and Gynecology,West China Second University Hospital,Sichuan University,Chengdu 610041,China;Key Laboratory of Birth Defects and Related Women and Children Diseases of the Ministry of Education(Sichuan University),Chengdu 610041,China)

机构地区：[1]四川大学华西第二医院妇产科教研室,成都610041 [2]出生缺陷与相关妇儿疾病教育部重点实验室(四川大学),成都610041

出　　处：《四川大学学报（医学版）》2021年第1期117-123,共7页Journal of Sichuan University(Medical Sciences)

基　　金：国家重点研发计划(No.2018YFC10022003);四川省科技厅重点研发项目(No.2017SZ0125)资助。

摘　　要：目的探讨比较基因组杂交微阵列(array-based comparative genomic hybridization,a-CGH)技术在高龄孕妇产前诊断胎儿染色体异常中的临床意义。方法选取因单纯高龄因素孕期行羊膜腔穿刺采集羊水标本进行产前检查诊断的孕妇3 677例为研究对象,采用CGXTM(8X60K)芯片对采集的羊水标本进行a-CGH检测,并采用Genoglyphix~?软件进行分析。结果 3 677例孕妇羊水标本中,a-CGH分析共检出染色体异常75例,异常率为2.04%,其中非整倍体40例(21-三体22例,18-三体5例,XXY 8例,XYY 3例,X/XX 2例),占53.33%;致病性拷贝数变异(copy number variations,CNVs)24例(19例为微缺失,5例为微重复,片段大小为323~26 780 kb),占32.00%;可能致病CNVs 11例(4例为微缺失,7例为微重复,片段大小为358~16 873 kb),占14.67%。此外,检出不明意义CNVs 31例,占总数的0.84%。高龄孕妇年龄每增长一岁,染色体非整倍体检出率明显增高(P<0.05),但致病性CNVs检出率在各年龄段差异无统计学意义(P>0.05)。结论 a-CGH不仅可以检测非整倍体异常,还可以检出微缺失/微重复综合征等染色体拷贝数变异。胎儿染色体非整倍体的发生率与年龄密切相关,但染色体拷贝数变异发生率与年龄无显著相关性。Objective To evaluate the clinical application of array-based comparative genomic hybridization(a-CGH)in the prenatal diagnosis of fetal chromosomal aberrations in gravidas with advanced maternal age(AMA).Methods A total of 3677 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to AMA were selected.Array-CGH was performed on the Agilent CGXTM(8 X60 K)platform and the data were analyzed by the Genoglyphix software.Results The overall detection rate of chromosomal aberration was2.04%(75/3677),with 53.33%(40/75)being aneuploidies,including 22 cases of trisomy-21,5 cases of trisomy-18,8 cases with XXY,3 cases of XYY and 2 cases of mosaic monosomy X,32.00%(24/75)being pathogenic copy number variations(pCNVs),including 19 cases of microdeletion and 5 cases of microduplication,with the fragment size ranging from 323 kb to 26780 kb,and 14.67%(11/75)being likely pathogenic CNVs(lpCNVs),including 7 cases of microdeletion and 7 cases of microduplication,with the fragment size ranging from 358 kb to 16873 kb.Besides,the detection rate of CNVs of unknown clinical significance(VUS)was 0.84%(31/3677).The detection rate of aneuploidies increased significantly with increased maternal age(P<0.05).However,there were no significant differences in the detection rate of p/lpCNVs among different maternal age groups(P>0.05).Conclusion Our findings suggest that,compared with traditional karyotype analysis,a-CGH not only detects aneuploidies,but also detect pathogenic CNVs,including microdeletion/microduplication syndromes.The detection rate of fetal aneuploidies was closely correlated to maternal age.However,no correlation was found between the detection rate of p/lpCNVs and maternal age.

关 键 词：染色体微阵列分析 比较基因组杂交微阵列 拷贝数变异 染色体非整倍体 高龄 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学]