title: Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma.
abstract: BACKGROUND
  Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A.
  
  
  RESULTS
  A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95% confidence interval: 23.2-206.7], respectively.
  
  
  CONCLUSIONS
  Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.
authors: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.
authors: Ji Hyae
authors: JH
authors: Lim
authors: Shin Young
authors: SY
authors: Kim
authors: So Yeon
authors: SY
authors: Park
authors: Shin Yeong
authors: SY
authors: Lee
authors: Mi Jin
authors: MJ
authors: Kim
authors: You Jung
authors: YJ
authors: Han
authors: Si Won
authors: SW
authors: Lee
authors: Jin Hoon
authors: JH
authors: Chung
authors: Moon Young
authors: MY
authors: Kim
authors: Jae Hyug
authors: JH
authors: Yang
authors: Hyun Mee
authors: HM
authors: Ryu
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D044127:Epigenesis, Genetic; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood* / Q000235:genetics*; D012372:ROC Curve; D017422:Sequence Analysis, DNA
chemical_list: D015105:3',5'-Cyclic-AMP Phosphodiesterases; C116137:PDE9A protein, human