2398例孕妇外周血游离胎儿DNA产前筛查阳性结果的验证与分析  

Confirmation and analysis of 2 398 positive results of cell-free fetal DNA

作　　者：赵军红[1] 代鹏[1] 朱若男[1] 时盼来 孟静静[1] 孔祥东[1] Zhao Junhong;Dai Peng;Zhu Ruonan;Shi Panlai;Meng Jingjing;Kong Xiangdong(The Genetics and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院妇产科遗传与产前诊断中心,450052

出　　处：《中华妇产科杂志》2020年第10期679-684,共6页Chinese Journal of Obstetrics and Gynecology

基　　金：国家重点研发计划子课题(2018YFC1002206-2)。

摘　　要：目的探讨孕妇外周血游离胎儿DNA(cff-DNA)产前筛查技术提示胎儿染色体异常的准确性和临床应用价值。方法收集2013年5月至2019年12月在郑州大学第一附属医院因cff-DNA产前筛查提示胎儿染色体异常而行侵入性产前诊断的2398例单胎孕妇的产前诊断结果。羊膜腔穿刺术后,2398例羊水标本均采集羊水细胞,采用荧光定量PCR(QF-PCR)技术和染色体核型分析技术进行检测,其中359例提示其他染色体异常标本同时行单核苷酸多态性微阵列(SNP array)分析。结果2398例孕妇cff-DNA产前筛查提示21三体987例、18三体351例、13三体135例、性染色体非整倍体(SCA)异常566例、其他染色体异常359例,经染色体核型分析检测出21三体826例、18三体213例、13三体17例,性染色体异常221例、其他染色体异常26例,检出率分别为83.69%(826/987)、60.68%(213/351)、12.59%(17/135)、39.04%(221/566)、7.24%(26/359)。QF-PCR检出三体核型1046例、性染色体异常188例,检出率分别为99.05%(1046/1056)、85.07%(188/221)。359例其他染色体异常经SNP array检测,有64例与cff-DNA筛查结果相符,检出率为17.83%(64/359),较染色体核型分析的检出率提高10.59%。结论染色体核型分析技术是诊断染色体数目异常的“金标准”。QF-PCR技术可作为常见三体和SCA异常的辅助检测技术。性染色体嵌合体发生率较高,应警惕漏诊。cff-DNA产前筛查提示染色体片段缺失或重复时建议首选SNP array技术验证。Objective To explore the clinical application value and accuracy of cell-free fetal DNA(cff-DNA)technique in prenatal screening.Methods The results of quantitative fluorescent PCR(QF-PCR)and karyotype of amniotic fluid cells were analyzed retrospectively in 2398 monocyesis pregnant women who had been amniocentesis at the First Affiliated Hospital of Zhengzhou University from May 2013 to December 2019,and the results of 359 cases who had been examined by single-nucleotide polymorphism array(SNP array).Results Cff-DNA test of 2,398 cases indicated 987 cases of trisomy 21,351 cases of trisomy 18,135 cases of trisomy 13,566 cases of sex chromosome abnormality,and 359 cases of other chromosome abnormality.Chromosome karyotype analysis detected 826 cases of trisomy 21,213 cases of trisomy 18,17 cases of trisomy 13,221 cases of sex chromosome abnormality,and 26 cases of other chromosome abnormality.The detection rate were 83.69%(826/987),60.68%(213/351),12.59%(17/135),39.04%(221/566)and 7.24%(26/359),respectively.QF-PCR detected 1046 cases of trisomy and 188 cases of sex chromosomes abnormality,and the detection rate was 99.05%(1046/1056)and 85.07%(188/221),respectively.Compared with the abnormal number detected by chromosome karyotype analysis,10 cases of trisomeric chimerism and 24 cases of sex chromosome were missed by QF-PCR.Among the 359 other chromosomal abnormalities detected by SNP array,64 cases were consistent with the results of cff-DNA,and the detection rate was 17.83%(64/359),which was 10.59%higher than the karyotype result.Conclusions Karyotype analysis is the gold standard for diagnosing chromosomal abnormalities.QF-PCR could diagnose common chromosome aneuploidy rapidly and accurately,and it could be used as an auxiliary detection technique for karyotype analysis.The incidence of sex chromosome chimerism is high,so missed diagnosis should be warned.SNP array could be given priority to verify chromosome microdeletion or microduplication detected by cff-DNA.

关 键 词：产前诊断 基因检测 染色体畸变 多态性 单核苷酸 聚合酶链反应 

分 类 号：R714.5[医药卫生—妇产科学]