摘要
目的探讨大规模平行测序无创基因检测在胎儿染色体非整倍体异常产前诊断中的临床应用价值。方法选择预约做产前诊断的高危孕妇914例,按危险因素分为唐氏综合征筛查高危组563例,高龄妊娠组245例和其他原因组106例。抽取孕妇外周血,提取血浆DNA,制备测序文库,用高通量测序仪器检测,结果与人类的参考基因组比对;同时采集胎儿羊水,经细胞培养后行羊水细胞染色体核型分析。结果 914例孕妇经大规模平行测序技术检出21-三体综合征高风险8例,18-三体综合征高风险3例,13-三体综合征高风险1例;与染色体核型分析相比,产前无创基因检测21-三体综合征、18-三体综合征、13-三体综合征的阳性预测值均为100%,而假阳性率均为0。914例样本中,检出45,X高风险3例、47,XXX和47,XXY高风险各2例;与染色体核型分析相比,产前无创基因检测45,X的假阳性率为0.11%,阳性预测值为66.7%,47,XXY和47,XXX的假阳性率均为0.22%,阳性预测值均为50%。结论大规模平行测序技术对胎儿常染色体非整倍体疾病的诊断,具有极高的阳性预测值,但对胎儿性染色体非整倍体异常的阳性预测值较低;只能作为一种高级筛查性检测而不是确诊方法。
Objective To assess the clinical value of massively parallel sequencing in diagnosis of fetal chromosomal aneuploidy. Methods Nine hundred and fourteen high - risk pregnant women registered in prenatal diagnostic centers of Hangzhou First People＇s Hospital were enrolled in the study. The plasma DNA was extracted and sequenced with high - throughput sequencing procedure. The results were compared with the human reference gene - database and statistically analyzed. Simultaneously, the cells isolated from the fetal amniotic fluid were cultured, and chromosomal karyotyping was performed to identify the chromosome aneuploidy. Results Among 914 pregnant women, 8 cases of trisomy 21,3 cases of trisomy 18,1 case of trisomy 13 were detected by massively parallel sequencing, which were in full accord with the results of chromosomal karyotype analysis. In addition 3 cases of 45, X, 2 cases of 47, XXX and 2 cases of 47, XXY were detected by massively parallel sequencing technology; with chromosomal karyotype analysis as gold standard the positive predictive value of non-invasive prenatal testing was 66.7% for 45, X, 50% for 47, XXX and 47, XXY, while the false positive rate was 0.11% for 45X, 0.22% for 47,XXX and 47, XXY. Conclusion Massively parallel sequencing technology is of high positive predictive value for de-tecting trisomy 21, 18, 13 and of low positive predictive value for detecting sex chromosome aneuploidies in prenatal diagnosis of the fetus chromosome aneuploidy, indicating that it may be used as an advanced screening test not as diagnostic method.
作者
王海
周蕾
王克义
怀磊
WANG Hai;ZHOU Lei;WANG Keyi;et al(Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China)
出处
《浙江医学》
CAS
2018年第1期12-15,共4页
Zhejiang Medical Journal
基金
浙江省人口计划生育科研项目(2014KYA237)
浙江省科技厅公益技术应用研究项目(2017C37150)
杭州市社会发展科研自主申报项目(20160533B13)
关键词
染色体非整倍体异常
大规模平行测序技术
无创产前检测
无创产前诊断
Chromosome aneuploid abnormality Massively parallel sequencing technology Non-invasive prena-tal testing Non-invasive prenatal diagnosis
