Genome-Wide Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing
Genome-Wide Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing
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DOI：
10.1097/aog.0b013e31824fb482
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发表时间：
2012-05-01
影响因子：
7.2
通讯作者：
Rava, Richard P.
中科院分区：
文献类型：
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作者：
Bianchi, Diana W.;Platt, Lawrence D.;Rava, Richard P.
目的：前瞻性地评价大规模平行测序检测孕妇血浆中胎儿全染色体非整倍体的诊断准确性。方法：采用前瞻性、盲法研究方法，采集美国60个地点2882名接受产前诊断的妇女的血样。一名独立的生物统计学家选择了所有核型异常的单胎妊娠，并随机选择了数量均衡的整倍体核型妊娠。结果：在532例分析队列中，89例三体21例中89例(敏感度100%，95%可信区间95.9~100)，36例三体中35例(敏感度97.2%，95%可信区间85.5~99.9)，14例三体中11例(敏感度78.6%，95%可信区间49.2~99.9)，233例女性中232例(敏感度99.6%，敏感度99.6%，敏感度97.2%，95%可信区间85.5~99.9)。男性184例，敏感度100%，95%可信区间98.0~100；16例单体X染色体15例，敏感度93.8%，95%可信区间69.8~99.8。常染色体非整倍体检测无假阳性结果(特异度100%，95%可信区间98.5~100)。此外，21三体嵌合体(3/3)、18三体嵌合体(1/1)和X单体嵌合体(2/7)、3例易位三体、2例其他常染色体三体(20和16)以及其他性染色体非整倍体(XXX、XXY和XYY)被正确分类。检测21、18、13三体和X单体的高度敏感性和特异性表明，大规模并行测序可以结合到现有的非整倍体筛查算法中，以减少不必要的侵入性操作。
OBJECTIVE: To prospectively determine the diagnostic accuracy of massively parallel sequencing to detect whole chromosome fetal aneuploidy from maternal plasma.METHODS: Blood samples were collected in a prospective, blinded study from 2,882 women undergoing prenatal diagnostic procedures at 60 U.S. sites. An independent biostatistician selected all singleton pregnancies with any abnormal karyotype and a balanced number of randomly selected pregnancies with euploid karyotypes. Chromosome classifications were made for each sample by massively parallel sequencing and compared with fetal karyotype.RESULTS: Within an analysis cohort of 532 samples, the following were classified correctly: 89 of 89 trisomy 21 cases (sensitivity 100%, 95% [confidence interval] CI 95.9-100), 35 of 36 trisomy 18 cases (sensitivity 97.2%, 95% CI 85.5-99.9), 11 of 14 trisomy 13 cases (sensitivity 78.6%, 95% CI 49.2-99.9), 232 of 233 females (sensitivity 99.6%, 95% CI 97.6 to more than 99.9), 184 of 184 males (sensitivity 100%, 95% CI 98.0-100), and 15 of 16 monosomy X cases (sensitivity 93.8%, 95% CI 69.8-99.8). There were no false-positive results for autosomal aneuploidies (100% specificity, 95% CI more than 98.5 to 100). In addition, fetuses with mosaicism for trisomy 21 (3/3), trisomy 18 (1/1), and monosomy X (2/7), three cases of translocation trisomy, two cases of other autosomal trisomies (20 and 16), and other sex chromosome aneuploidies (XXX, XXY, and XYY) were classified correctly.CONCLUSION: This prospective study demonstrates the efficacy of massively parallel sequencing of maternal plasma DNA to detect fetal aneuploidy for multiple chromosomes across the genome. The high sensitivity and specificity for the detection of trisomies 21, 18, 13, and monosomy X suggest that massively parallel sequencing can be incorporated into existing aneuploidy screening algorithms to reduce unnecessary invasive procedures.