title: Non-invasive prenatal detection of fetal trisomy 18 by RNA-SNP allelic ratio analysis using maternal plasma SERPINB2 mRNA: a feasibility study.
abstract: OBJECTIVE
  Non-invasive prenatal diagnosis of chromosome aneuploidies has been achieved by measuring the ratio of two alleles of a single nucleotide polymorphism (SNP) in circulating placental mRNA (the RNA-SNP allelic ratio approach) in maternal plasma. We investigated the feasibility of applying this approach for the non-invasive prenatal detection of fetal trisomy 18.
  
  
  METHODS
  We targeted serpin peptidase inhibitor, clade B (ovalbumin), membrane 2 (SERPINB2) mRNA, which is transcribed from chromosome 18 and is preferentially expressed by the placenta. We developed a mass-spectrometric assay to measure the SERPINB2 RNA-SNP allelic ratios in the placental samples and maternal plasma obtained from pregnancies involving euploid and trisomy 18 fetuses.
  
  
  RESULTS
  We were able to separate all the euploid and trisomy 18 placentas by their SERPINB2 RNA-SNP allelic ratios. The allelic ratios of the trisomy 18 placentas deviated from the reference interval established from the euploid placentas. Due to the relatively low concentrations of SERPINB2 mRNA in maternal plasma, we used pooled maternal plasma samples for analysis. We were able to identify three of the four pooled trisomy 18 plasma samples by their deviated allelic ratios when compared with the reference interval obtained from pooled euploid plasma samples.
  
  
  CONCLUSIONS
  It is feasible to detect fetal trisomy 18 non-invasively by maternal plasma SERPINB2 RNA-SNP analysis provided that sufficient quantities of plasma samples are used.
authors: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors: Nancy B Y
authors: NB
authors: Tsui
authors: Blenda C K
authors: BC
authors: Wong
authors: Tak Y
authors: TY
authors: Leung
authors: Tze K
authors: TK
authors: Lau
authors: Rossa W K
authors: RW
authors: Chiu
authors: Y M Dennis
authors: YM
authors: Lo
mesh_terms: D000483:Alleles; D001774:Blood Chemical Analysis / Q000379:methods; D002887:Chromosomes, Human, Pair 18; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D009035:Mothers; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood / Q000235:genetics; D011296:Prenatal Diagnosis / Q000379:methods*; D012333:RNA, Messenger / Q000032:analysis* / Q000097:blood / Q000235:genetics; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*
chemical_list: D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger