title: Identification of new biomarkers for Down's syndrome in maternal plasma.
abstract: Using ProteinChip Technology (SELDI TOF MS), the maternal plasma of 53 chromosomally-normal control and 28 Down's syndrome affected pregnancies was profiled between 10 and 20 weeks' gestation. Preliminary studies demonstrated two distinct phases of changes in protein expression, the first at 10-14 weeks and second at 14-20 weeks. Using this data, analysis of the 10-14 weeks' plasma samples (Down's syndrome n=13, control n=20) showed the presence of a protein of mass 100.3 kDa that was elevated in the Down's syndrome group compared to the controls (p<0.002). This protein was further isolated using SAX Q-spin columns and identified using QTOF MS and Western blotting as being plasma protease C1-inhibitor. Analysis of the 14-20 week cohort demonstrated changes in protein expression of three additional proteins. Two of these proteins were found to be up-regulated (serum amyloid P-component, p<0.004 and transthyretin, p<0.006) and complement C3-α chain was observed to be down-regulated (p<0.0005). The identification of these biomarkers in maternal plasma and their potential to improve current Down's syndrome screening are discussed.
authors.affiliation: Clinical & Molecular Genetics Unit, UCL Institute of Child Health, University College London, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Heywood
authors.forename: Kevin
authors.initials: K
authors.lastname: Mills
authors.forename: Darrell
authors.initials: D
authors.lastname: Wang
authors.forename: Julie
authors.initials: J
authors.lastname: Hogg
authors.forename: Tracey E
authors.initials: TE
authors.lastname: Madgett
authors.forename: Neil D
authors.initials: ND
authors.lastname: Avent
authors.forename: Lyn S
authors.initials: LS
authors.lastname: Chitty
mesh_terms: D015415:Biomarkers / Q000097:blood*; D050718:Complement C1 Inhibitor Protein / Q000032:analysis*; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D011228:Prealbumin / Q000032:analysis; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*; D000683:Serum Amyloid P-Component / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D050718:Complement C1 Inhibitor Protein; D011228:Prealbumin; D000683:Serum Amyloid P-Component