Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, King's College, University of London, London, England, UK.
Am J Obstet Gynecol. 2012 Apr;206(4):322.e1-5. doi: 10.1016/j.ajog.2012.01.029. Epub 2012 Jan 24.
The purpose of this study was to assess the prenatal detection rate of trisomy 21 and 18 and the false-positive rate by chromosome-selective sequencing of maternal plasma cell-free DNA.
Nested case-control study of cell-free DNA was examined in plasma that was obtained at 11-13 weeks before chorionic villous sampling from 300 euploid pregnancies, 50 pregnancies with trisomy 21, and 50 pregnancies with trisomy 18. Laboratory personnel were blinded to fetal karyotype.
Risk scores for trisomy 21 and 18 were given for 397 of the 400 samples that were analyzed. In all 50 cases of trisomy 21, the risk score for trisomy 21 was ≥ 99%, and the risk score for trisomy 18 was ≤ 0.01%. In all 50 cases of trisomy 18, the risk score for trisomy 21 was ≤ 0.01%, and the risk score for trisomy 18 was ≥ 99% in 47 cases, 98.8% in 1 case, 88.5% in 1 case, and 0.11% in 1 case. In 3 of the 300 euploid pregnancies (1%), no risk score was provided, because there was failed amplification and sequencing. In the remaining 297 cases, the risk score for trisomy 21 was ≤ 0.01%, and the risk score for trisomy 18 was ≤ 0.01% in 295 cases, 0.04% in 1 case, and 0.23% in 1 case. Therefore, the sensitivity for detecting trisomy 21 was 100% (50/50 cases); the sensitivity for trisomy 18 was 98% (49/50 cases), and the specificity was 100% (297/297 cases).
In this study, chromosome-selective sequencing of cell-free DNA separated all cases of trisomy 21 and 98% of trisomy 18 from euploid pregnancies.
本研究旨在评估通过母体外周血游离 DNA 染色体选择性测序检测 21 三体和 18 三体的产前检出率和假阳性率。
对 300 例正常核型妊娠、50 例 21 三体和 50 例 18 三体孕妇在绒毛活检前 11-13 周采集的血浆游离 DNA 进行巢式病例对照研究。实验室人员对胎儿核型进行盲法检测。
对 400 例分析样本中的 397 例进行了 21 三体和 18 三体风险评分。在所有 50 例 21 三体中，21 三体的风险评分均≥99%，18 三体的风险评分均≤0.01%。在所有 50 例 18 三体中，21 三体的风险评分均≤0.01%，47 例评分均≥99%，1 例评分 98.8%，1 例评分 88.5%，1 例评分 0.11%。在 300 例正常核型妊娠中（1%），有 3 例因扩增和测序失败而未提供风险评分。在其余 297 例中，21 三体的风险评分均≤0.01%，18 三体的风险评分均≤0.01%，295 例评分均≤0.01%，1 例评分 0.04%，1 例评分 0.23%。因此，21 三体的检出率为 100%（50/50 例）；18 三体的检出率为 98%（49/50 例），特异性为 100%（297/297 例）。
在本研究中，游离 DNA 染色体选择性测序将所有 21 三体和 98%的 18 三体病例与正常核型妊娠区分开来。
