目的 探讨孕妇血浆中游离胎儿DNA 高通量基因测序技术(NIPT)在常州地区产前筛查中的临床应用经验总结及推广。方法 选择2012年10月至2016年3月在常州市妇幼保健院产前诊断中心就诊的6505例单胎孕妇在知情同意的情况下抽取孕妇外周血10ml,4小时内分离血浆中游离DNA建立文库，采用Illumina Nextseq CN500测序平台对其进行测序分析，对测序结果进行生物信息分析，提示染色体异常患者再行羊膜腔穿刺，羊水细胞培养后染色体G显带核型分析。对确诊患者建议终止妊娠。结果 6505例检测样本中NIPT结果提示有97例胎儿染色体异常，其中81例孕妇自愿接受羊水穿刺。①胎儿常染色染色体非整倍体49例（T21 43例，T18 5例，T13 1例），羊水培养核型分析后发现：T21阳性预测值达95.1%，T18 4例确诊（4/5), T13 1例确诊（1/1）；②32例性染色体非整倍体异常，其阳性预测值达53.1%，包括：14例45,XO高风险中仅确诊4例，假阳性10例；12例47，XXY高风险，进一步确诊发现8例，4例假阳性；最后确诊2例47,XXX和2例47，XXY。结论 NIPT技术在唐氏综合征筛查上准确性高、假阳性率低；T18，T13样本少无统计学上意义。在性染色体数目筛查方面，结果准确性偏低，特别体现在Turner综合征，故对45,XO筛查结果在遗传咨询须谨慎处理。
Objective To explore the clinical performance of massively parallel sequencing-based non-invasive prenatal testing (NIPT) in Changzhou in China. Method A total of 6505 maternal blood samples were collected from Oct 2012 to Mar 2016 at the prenatal diagnosis center of Changzhou maternal and child health care hospital. The peripheral venous blood from the pregnancies was drawn, plasma cell-free fetal DNA was extracted in 4 hours after sampling, the sequencing library was established. High-throughput sequencing procedure was carried out on Illumina NextSeq500 platform. The pregnancies with fetal chromosomal abnormalities were advised to accept prenatal fetal chromosomal karyotype analysis of amniotic fluid cells using G-banding technique. Results High-throughput sequencing detected 97 pregnancies with fetal chromosomal aneuploidies in 6505 pregnancies. After receiving informed consent, 81 voluntarily accepted amniotic fluid prenatal diagnosis. ① 49 were autosomal chromosome aneuploidy ( of which 43 cases were trisomy 21, 5 cases were trisomy 18, and 1 case was trisomy 13) by NIPT. The positive predictive value for trisomy 21was 95.1%. 4 cases were diagnosed as trisomy 18 and 1 case was diagnosed as trisomy 13.②The positive predictive value for sex chromosomal abnormalities was 53.1%. Among 14 positive cases of 45,X by NIPT, there were only 4 true positive cases confirmed by amniotic fluid prenatal diagnosis. There were 12 cases of 47,XXY by NIPT, only 8 cases were confirmed by amniotic fluid prenatal diagnosis . 3 positive cases of 47,XXX and 2 positive cases of 47,XYY also confirmed. Conclusions The use of NIPT for DS was high accuracy and low false positive rate. however, the accuracy of sex chromosomal aneuploidies was very low, especially for Turner’s syndrome. Genetic counseling should be handled with care.
