title: Elevated levels of total (maternal and fetal) beta-globin DNA in maternal blood from first trimester pregnancies with trisomy 21.
abstract: 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), beta-globin (11p15.5), beta-actin (7p15-12) and p53 (17p13.1).
  
  
  RESULTS
  Beta-globin DNA levels were significantly elevated (P = 0.003) in 13 of 17 trisomy 21 cases (4.08 +/- 1.78 Geq/ml x 10(5)) compared with matched controls (2.35 +/- 1.84 Geq/ml x 10(5)). Following conversion of beta-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, beta-actin and p53 sequences were detected.
  
  
  CONCLUSIONS
  This work demonstrates differential levels of circulating beta-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. Beta-globin in particular is an attractive biomarker that could contribute to enhance multiple serum parameter testing in the first trimester.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, 2450 Holcombe Blvd, Houston, TX 77054, USA.
authors.forename: Carolina J
authors.initials: CJ
authors.lastname: Jorgez
authors.forename: Dianne D
authors.initials: DD
authors.lastname: Dang
authors.forename: Ronald
authors.initials: R
authors.lastname: Wapner
authors.forename: Antonio
authors.initials: A
authors.lastname: Farina
authors.forename: Joe Leigh
authors.initials: JL
authors.lastname: Simpson
authors.forename: Farideh Z
authors.initials: FZ
authors.lastname: Bischoff
mesh_terms: D000293:Adolescent; D000328:Adult; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005914:Globins / Q000235:genetics*; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D005914:Globins; D004247:DNA