Down syndrome and cell-free fetal DNA in archived maternal serum.
Down syndrome and cell-free fetal DNA in archived maternal serum.
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DOI：
10.1067/mob.2002.127462
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发表时间：
2002-11
影响因子：
9.8
通讯作者：
Thomas Lee;Erik S. Leshane;G. Messerlian;J. Canick;A. Farina;W. Heber;D. Bianchi
中科院分区：
文献类型：
--
作者：
Thomas Lee;Erik S. Leshane;G. Messerlian;J. Canick;A. Farina;W. Heber;D. Bianchi
目的母体循环中胎儿游离DNA（f-DNA）水平的升高是胎儿唐氏综合征的潜在非侵入性标志。我们的目的是（1）确定是否可以通过使用存档的血清和羊水定量f-DNA，（2）检查是否血清f-DNA水平升高唐氏综合征妊娠在一个病例对照系列匹配的胎龄和样本储存时间，（3）确定是否f-DNA水平升高唐氏综合征胎儿的羊水。研究设计预先从怀有47，XY，+21胎儿的孕妇中收集并储存在-20 ℃下的11份血清和6份羊水样品，每个样品与来自怀有假定整倍体男性胎儿的孕妇的相同标本类型的5份匹配对照样品配对。通过实时聚合酶链反应扩增Y染色体序列盲法定量f-DNA浓度。采用配对秩和分析和方差分析进行分析。结果唐氏综合征组的平均观察等级为5.0，显著高于预期（P </=.005）。校正后的平均血清f-DNA浓度为41.2基因组当量（GE）每毫升的唐氏综合征病例和24.2 GE/mL的整倍体对照（P = 0.002）。羊水样本之间的差异无统计学意义。有证据表明，样本储存对f-DNA浓度的影响约为每月-0.66 GE/mL（P =.071）。结论唐氏综合征孕妇血清游离f-DNA水平是对照组的1.7倍。在羊水中没有观察到这种关联。存档血清似乎是用于回顾性分析的临床材料的有用来源，但可能需要控制样本储存的持续时间。
OBJECTIVE Increased levels of cell-free fetal DNA (f-DNA) in the maternal circulation are a potential noninvasive marker for fetal Down syndrome. Our objectives were to (1) determine whether f-DNA could be quantified by using archived serum and amniotic fluid, (2) examine whether serum f-DNA levels are elevated in Down syndrome pregnancies in a case-control series matched for gestational age and duration of sample storage, and (3) determine whether f-DNA levels are elevated in the amniotic fluid of Down syndrome fetuses. STUDY DESIGN Eleven serum and six amniotic fluid samples previously collected and stored at -20 degrees C from gravid women carrying a 47,XY,+21 fetus were each paired with five matched control samples of identical specimen type from gravid women carrying a presumed euploid male fetus. f-DNA concentration was quantified blindly by real-time polymerase chain reaction amplification for a Y-chromosome sequence. Matched rank-sum analysis and analysis of variance were used for analysis. RESULTS The mean observed rank of 5.0 in the Down syndrome group was significantly higher than expected (P </=.005). Adjusted mean serum f-DNA concentrations were 41.2 genomic equivalents (GE) per milliliter for the Down syndrome cases and 24.2 GE/mL for the euploid controls (P =.002). Differences among amniotic fluid samples were not statistically significant. There was a suggestion of a sample storage effect on f-DNA concentration on the order of -0.66 GE/mL per month (P =.071). CONCLUSION Down syndrome pregnancies exhibit 1.7-fold higher levels of maternal serum cell-free f-DNA compared with matched controls. No such association is observed in amniotic fluid. Archived serum appears to be a useful source of clinical material for retrospective analyses but may require controlling for the duration of sample storage.