Elevated levels of total (maternal and fetal) β-globin DNA in maternal blood from first trimester pregnancies with trisomy 21

• Published in: Human reproduction (Oxford) 2007-08, Vol.22 (8), p.2267-2272
• Main Authors: Jorgez, Carolina J., Dang, Dianne D., Wapner, Ronald, Farina, Antonio, Simpson, Joe Leigh, Bischoff, Farideh Z.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; cell-free fetal DNA; DNA - blood; Down Syndrome - blood; Down Syndrome - diagnosis; Down Syndrome - genetics; Female; Fetal Blood - chemistry; Globins - genetics; Gynecology. Andrology. Obstetrics; Humans; maternal dried blood spot; Medical sciences; non-invasive prenatal diagnosis; Pregnancy; Pregnancy Trimester, First - blood; Prenatal Diagnosis - methods; trisomy 21; β-globin
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dem154

BACKGROUND Elevated 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. METHODS Maternal 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). RESULTS β-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 of β-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. CONCLUSIONS This work demonstrates differential levels of circulating β-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.