Elevated levels of total (maternal and fetal) beta-globin DNA in maternal blood from first trimester pregnancies with trisomy 21.
Elevated levels of total (maternal and fetal) beta-globin DNA in maternal blood from first trimester pregnancies with trisomy 21.
复制标题
21 三体妊娠早期妊娠的母体血液中总（母体和胎儿）β-珠蛋白 DNA 水平升高。
DOI：
10.1093/humrep/dem154
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Bischoff,FaridehZ
中科院分区：
文献类型：
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作者：
Jorgez,CarolinaJ;Dang,DianneD;Wapner,Ronald;Farina,Antonio;Simpson,JoeLeigh;Bischoff,FaridehZ
当确认为21三体胎儿时，在母体血浆中观察到循环胎儿DNA水平升高。然而，这些研究仅限于携带男性胎儿的妊娠。我们试图量化干血斑（DBS）中的总（胎儿和母体）DNA，作为多参数产前非整倍体筛查的额外因素。方法母体DBS从NICHD赞助的多中心队列（BU N）研究中获得。17例确诊的21三体（平均胎龄12.23 ± 0.77周）病例均与整倍体对照组（n= 30）的胎龄相匹配。提取DNA，采用定量PCR方法检测21号染色体上的4个位点，包括甘油醛-3-磷酸脱氢酶（GAPDH）（12 p13）、β-珠蛋白（β-globin（11页15.5），β-actin（7 p15 -12）和p53（17p13.1）。结果β-珠蛋白DNA水平显著升高17例21三体患者中有13例（4.08 ± 1.78 Geq/ml × 105）与对照组（2.35 ± 1.84 Geq/ml × 105）相比，差异有统计学意义（P= 0.003）。将β-珠蛋白浓度转换为中位数倍数（MoM）后，21三体病例的MoM为2.8，而整倍体病例为1.0。循环GAPDH、β-actin和p53序列水平无显著差异。结论：本研究证实了整倍体和21三体患者母血中循环β-珠蛋白DNA水平的差异。序列特异性定量可以提供一种额外的措施，以改善产前筛查的非侵入性方法，以使用干血检测21三体。β-珠蛋白特别是一种有吸引力的生物标志物，可以有助于提高在妊娠早期的多个血清参数测试。
BACKGROUNDElevated levels of circulating fetal DNA have been observed in maternal plasma when a trisomy 21 fetus is confirmed. However, these studies have been limited to pregnancies carrying a male fetus. We sought to quantify total (fetal and maternal) DNA from dried blood spots (DBS) for use as an additional factor in multi-parameter prenatal screening for aneuploidy.METHODSMaternal DBS were obtained from the NICHD-sponsored multi-center cohort (BUN) study. Seventeen confirmed trisomy 21 (mean gestational age 12.23 ± 0.77 weeks) cases were each matched by gestational age to euploid controls (n= 30). DNA was extracted and quantitative PCR was performed to measure four non-chromosome 21 loci, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (12p13),β-globin (11p15.5),β-actin (7p15–12) and p53 (17p13.1).RESULTSβ-Globin DNA levels were significantly elevated (P= 0.003) in 13 of 17 trisomy 21 cases (4.08 ± 1.78 Geq/ml × 105) compared with matched controls (2.35 ± 1.84 Geq/ml × 105). Following conversion ofβ-globin concentrations into multiples of the median (MoM), MoM for trisomy 21 cases was 2.8 compared with 1.0 in euploid cases. No significant differences in levels of circulating GAPDH,β-actin and p53 sequences were detected.CONCLUSIONSThis work demonstrates differential levels of circulatingβ-globin DNA in maternal blood of euploid and trisomy 21 cases. Sequence-specific quantification could provide an additional measure to improve non-invasive methods of prenatal screening to detect trisomy 21 using dried blood.β-Globin in particular is an attractive biomarker that could contribute to enhance multiple serum parameter testing in the first trimester.