Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.
Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Prenat Diagn. 2018 May;38(6):445-458. doi: 10.1002/pd.5260.
Maternal plasma cell-free DNA (cfDNA) analysis is a powerful screening tool for Down syndrome. In a pilot series, we examined biologic causes of discordance between the cfDNA test results and the fetal karyotype. We also explored the feasibility of obtaining trio biospecimens by using parental engagement.
A convenience sample of women with discordant cfDNA results were recruited by their care providers. We provided shipping materials and instructions for biospecimen collection. Maternal, newborn, and placental samples were examined with droplet digital PCR.
Thirteen of 15 women successfully had biospecimens obtained remotely. High-quality DNA was extracted in 12 of 13 women. Presumed biologic etiologies for discordance were identified in 7 of 12 women: 3 cases from additional clinical review (male renal transplant, vanishing twin, and colon cancer) and 4 cases from additional laboratory investigation using droplet digital PCR (3 with confined placental mosaicism and 1 with true fetal mosaicism).
Understanding the biology behind cfDNA-fetal karyotype discordancy is useful for follow-up clinical care. Our study suggests that most cases could be resolved by using a trio biospecimen protocol and parental involvement. To improve accuracy, additional sequencing of biospecimens will be required.
母体血浆游离 DNA（cfDNA）分析是唐氏综合征的一种强大筛查工具。在一项试点研究中，我们研究了 cfDNA 检测结果与胎儿核型不一致的生物学原因。我们还探讨了通过父母参与获得三标本的可行性。
通过其护理提供者招募 cfDNA 结果不一致的女性进行便利抽样。我们提供了运输材料和生物标本采集说明。使用液滴数字 PCR 对母体、新生儿和胎盘样本进行了检查。
15 名女性中有 13 名成功远程获得了生物标本。13 名女性中有 12 名成功提取了高质量的 DNA。在 12 名女性中有 7 名确定了不一致的推定生物学病因：3 例来自额外的临床审查（男性肾移植、双胎消失和结肠癌），4 例来自使用液滴数字 PCR 的额外实验室调查（3 例为胎盘局限性嵌合体，1 例为真正的胎儿嵌合体）。
了解 cfDNA-胎儿核型不一致的生物学基础对于后续临床护理很有用。我们的研究表明，大多数病例可以通过使用三标本方案和父母参与来解决。为了提高准确性，需要对生物标本进行额外的测序。
