Laboratory Corporation of America, La Jolla, California, United States of America.
PLoS One. 2021 Mar 12;16(3):e0248467. doi: 10.1371/journal.pone.0248467. eCollection 2021.
Mosaicism ratio, or MR, is a laboratory metric that can be calculated using massively parallel sequencing data from cell-free DNA (cfDNA) screening. MR compares the amount of cfDNA present from a particular chromosome or chromosomal region to the overall fetal fraction of the specimen. In singleton gestations, MR may be used to refine the positive predictive value of an abnormal cfDNA screening result by identifying cases that could be impacted by various biological factors, such as placental mosaicism or prior co-twin demise. The current study was designed to examine the behavior of mosaicism ratio (MR) in multifetal gestations. Multifetal cfDNA specimens with positive results for trisomies 21, 18, or 13 and confirmed diagnostic outcomes were compiled to examine MR of the aneuploid chromosome based on the number of affected fetuses/placentas. A second multifetal cohort was assembled to analyze the MR of the Y chromosome in cases with at least one male fetus. For aneuploid cases, the average MR of affected singletons (used as a biological proxy for two affected twins) was significantly higher than the average MR for twins in which one fetus was affected. The average MR of the aneuploid chromosome for one affected twin was 52%, 42%, and 48% of that of singleton gestations for trisomy 21, 18, and 13 cases, respectively. MR cutoffs of 0.7 for trisomy 21, and 0.5 for trisomies 18 and 13 may help predict whether one versus both twins are affected with aneuploidy when clinical concern arises. For male cases, the Y MR of XX/XY gestations was 48% of the Y MR for XY/XY gestations. Using a Y MR cutoff of 0.8 allowed determination of XX/XY versus XY/XY gestations with 92.3-94.9% accuracy. Based on the data presented, MR may have utility in the analysis and interpretation of cfDNA data from multifetal gestations.
嵌合体率（MR）是一种实验室指标，可以使用来自游离胎儿 DNA（cfDNA）筛查的大规模平行测序数据进行计算。MR 比较特定染色体或染色体区域的 cfDNA 量与样本的总胎儿分数。在单胎妊娠中，MR 可用于通过识别可能受到各种生物学因素影响的病例（如胎盘嵌合体或先前的双胎死亡）来提高异常 cfDNA 筛查结果的阳性预测值。本研究旨在检查多胎妊娠中嵌合体率（MR）的行为。对三体 21、18 或 13 的阳性 cfDNA 筛查结果和确诊诊断结果的多胎 cfDNA 标本进行了汇编，以根据受影响的胎儿/胎盘数量检查非整倍体染色体的 MR。组装了第二个多胎队列来分析至少有一个男性胎儿的病例中 Y 染色体的 MR。对于非整倍体病例，受影响的单体（用作受影响的双胞胎的两个双胞胎的生物学代表）的平均 MR 明显高于受影响的双胞胎中一个胎儿受影响的平均 MR。三体 21、18 和 13 病例中，一个受影响的双胞胎的非整倍体染色体的平均 MR 分别为单体妊娠的 52%、42%和 48%。对于三体 21，截断值为 0.7，对于三体 18 和 13，截断值为 0.5，这可能有助于预测当出现临床关注时，是一个还是两个双胞胎受到非整倍体的影响。对于男性病例，XX/XY 妊娠的 Y-MR 是 XY/XY 妊娠的 Y-MR 的 48%。使用 Y-MR 截断值 0.8，可以以 92.3-94.9%的准确率确定 XX/XY 与 XY/XY 妊娠。基于呈现的数据，MR 可能在多胎妊娠的 cfDNA 数据分析和解释中具有实用性。
