Fetoplacental mosaicism: potential implications for false-positive and false-negative noninvasive prenatal screening results

被引:159
作者
Grati, Francesca R. [1 ]
Malvestiti, Francesca [1 ]
Ferreira, Jose C. P. B. [2 ]
Bajaj, Komal [2 ]
Gaetani, Elisa [1 ]
Agrati, Cristina [1 ]
Grimi, Beatrice [1 ]
Dulcetti, Francesca [1 ]
Ruggeri, Anna M. [1 ]
De Toffol, Simona [1 ]
Maggi, Federico [1 ]
Wapner, Ronald [3 ]
Gross, Susan [2 ]
Simoni, Giuseppe [1 ]
机构
[1] TOMA Adv Biomed Assays SpA, Res & Dev, Busto Arsizio, VA, Italy
[2] Albert Einstein Coll Med, Dept Obstet & Womens Hlth, Bronx, NY 10467 USA
[3] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY USA
关键词
cell-free placental DNA; false-negative rate; false-positive rate; fetoplacental mosaicism; noninvasive prenatal screening; FREE FETAL DNA; MATERNAL PLASMA; UNIPARENTAL DISOMY; ANEUPLOIDY;
D O I
10.1038/gim.2014.3
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Purpose: Noninvasive prenatal screening for fetal aneuploidy analyzes cell-free fetal DNA circulating in the maternal plasma. Because cell-free fetal DNA is mainly of placental trophoblast origin, false-positive and false-negative findings may result from placental mosaicism. The aim of this study was to calculate the potential contribution of placental mosaicism in discordant results of noninvasive prenatal screening. Methods: We performed a retrospective audit of 52,673 chorionic villus samples in which cytogenetic analysis of the cytotrophoblast (direct) and villus mesenchyme (culture) was performed, which was followed by confirmatory amniocentesis in chorionic Villi mosaic cases. Using cases in which cytogenetic discordance between cytotrophoblast and amniotic fluid samples was identified, we calculated the potential contribution of cell line-specific mosaicism to false-positive and false-negative results of noninvasive prenatal screening. Results: The false-positive rate, secondary to the presence of abnormal cell line with common trisomies in cytotrophoblast and normal amniotic fluid, ranged from 1/1,065 to 1/3,931 at 10% and 100% mosaicism, respectively; the false-negative rate was calculated from cases of true fetal mosaicism, in which a mosaic cell line was absent in cytotrophoblast and present in the fetus; this occurred in 1/107 cases. Conclusion: Despite exciting advances, underlying biologic mechanisms will never allow 100% sensitivity or specificity.
引用
收藏
页码:620 / 624
页数:5
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