Effective detection of fetal sex using circulating fetal DNA in first-trimester maternal plasma.

Ji Hyae Lim; So Yeon Park; Shin Young Kim; Do Jin Kim; Ji Eun Choi; Min Hyoung Kim; Jun Seek Choi; Moon Young Kim; Jae Hyug Yang; Hyun Mee Ryu

The aim of this study was to develop a simple and effective method for noninvasively detecting fetal sex using circulating fetal DNA from first-trimester maternal plasma. A study was conducted with maternal plasma collected from 203 women between 5 and 12 wk of gestation. The presence of circulating fetal DNA was confirmed by a quantitative methylation-specific polymerase chain reaction of the unmethylated-PDE9A gene (U-PDE9A). Multiplex real-time PCR was used to simultaneously quantify the amount of DYS14 and GAPDH in maternal plasma. The results were confirmed by phenotype at birth. Pregnancy outcomes and U-PDE9A concentrations were obtained in all cases, including 99 male-bearing and 104 female- bearing participants. At equivalent specificity (100%), the false-negative rate was 9.1% for DYS14 quantification cycle, 7.1% for DYS14 concentration, and 0.0% for the concentration ratio of DYS14/GAPDH, respectively. In male-bearing participants, DYS14, U-PDE9A, and GAPDH concentrations were significantly lower in the false-negative case than in correct case (P≥ 0.001 in all). Moreover, DYS14, U-PDE9A, and GAPDH concentrations showed significantly positive associations with each other (P<0.001 in all). The ratio of DYS14/ GAPDH in maternal plasma was an effective biomarker for noninvasive fetal sex detection during the first trimester, indicating that it could be useful for clinical application.

EPIGENETICS; POLYMERASE chain reaction; BIOMARKERS; DNA polymerases; DNA; DIAGNOSTIC sex determination; METHYLATION

FASEB Journal, 2012, Vol 26, Issue 1, p250

0892-6638

Academic Journal

10.1096/fj.11-191429