高通量测序技术在无创性产前胎儿染色体缺失重复检测中的应用

Application of high-throughput sequencing technology in noninvasive prenatal detection of fetal chromosomal deletion and duplication

目的:探讨高通量测序技术在无创性产前胎儿染色体缺失重复检测中应用效果。方法:收集2016年8月—2018年8月本院行无创产前检测的自然受孕单胎孕妇5170例,在孕12~22周采集孕妇外周静脉血行无创性产前胎儿染色体检测,对提示染色体缺失重复者行产前遗传咨询,经孕妇及其家人知情同意后孕18~24周行羊水细胞培养染色体核型分析和微阵列检测,分析无创性产前胎儿染色体检测与染色体核型及微阵列分析结果的符合率。结果:无创产前检查提示染色体缺失重复病例27例均接受了羊水穿刺,检出染色体异常11例,其中9例与染色体微阵列结果相符(33.3%);不相符2例微阵列结果提示为多态性。无创产前检查提示性染色体异常12例中11例接受羊水穿刺,检出胎儿性染色体异常7例,符合率63.64%。结论:高通量测序无创性产前检测技术对产前胎儿染色体缺失重复的筛查具有临床价值,但针对染色体缺失重复及性染色体异常检测的临床符合率不高,当提示染色体异常时必须行有创性产前诊断(染色体核型分析或微阵列分析)。

Objective:To investigate the application effect of high-throughput sequencing technology in noninvasive prenatal detection of fetal chromosomal deletion and duplication.Methods:5170 pregnant women with natural conception and single fetus were selected in the study from August 2016 to August 2018.The noninvasive prenatal detection were performed in all the included women at 12-22 gestational weeks for screening their fetal chromosomal abnormalities.Among them,the women with high risk of fetal chromosomal deletion and duplication were accepted prenatal genetic counseling and the chromosome karyotype analysis and microarray detection of amniotic fluid cell culture were further performed at 18-24 gestational weeks after informed consent by pregnant women and their families.The coincidence rate of noninvasive prenatal fetal chromosome detection with chromosome karyotype and microarray analysis results were conducted.Results:There were 27 cases of autosomal duplication and deletion and 12 cases of sexual chromosomal abnormalities detected by noninvasive prenatal testing from the 5170 pregnant women.The 27 women with fetal autosomal deletion and duplication had received amniocentesis chromosome karyotype and microarray analysis,and 11(33.3%)women with fetal chromosomal abnormalities were confirmed,which included 9 cases consistent with the results of chromosomal microarray,and 2 cases with polymorphism.11 of the 12 cases with fetal sexual chromosomal abnormalities by noninvasive prenatal examination had received amniocentesis chromosome karyotype and microarray analysis,and 7 cases were confirmed by chromosomal microarray,which coincidence rate was 63.64%.Conclusion:Noninvasive prenatal DNA detection by high-throughput generation sequencing technology has some clinical value in screening fetus chromosomal deletion and duplication.However,the clinical coincidence rate of chromosomal deletion and duplication and sexual chromosomal abnormalities is not very high,so it is necessary of the invasive chromosomal karyotype and microarray analysis for pregnant women with high risk of chromosomal abnormalities by noninvasive prenatal DNA detection.