BACKGROUND: Despite the large impact of ultrasonographic and biochemical markers on prenatal screening, the ability to accurately diagnose Down syndrome (DS) is still limited and better diagnostic testing is needed. METHODS: Plasma from 8 women carrying a DS foetus and 12 with non-DS foetuses matched for gestational age, maternal age and ethnicity, in the second trimester of pregnancy, was analysed by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in order to identify biomarkers for DS. RESULTS: Gel comparison revealed nine proteins differentially expressed in maternal plasma in women with DS foetuses. Eight proteins, transthyretin (TTHY), ceruloplasmin (CERU), afamin (AFAM), alpha-1-microglobulin (AMBP), apolipoprotein E (APOE), serum amyloid P-component (SAMP), histidine-rich glycoprotein (HRG) and alpha-1-antitrypsin (A1AT) were up-regulated and one, clusterin (CLUS), down-regulated. All nine proteins are known to be involved in foetal growth and development. APOE, SAMP, AFAM and CLUS are associated with the DS phenotype. Western blot and densitometric analysis of APOE and SAMP confirmed the increase of both proteins by 19 and 48% respectively. CONCLUSIONS: All differentially expressed proteins are candidate biomarkers for DS, providing opportunities for the development of non-invasive prenatal diagnosis. As these are preliminary findings, follow-up experiments are needed for their evaluation. Copyright (c) 2008 John Wiley & Sons, Ltd.
BACKGROUND: Despite the large impact of ultrasonographic and biochemical markers on prenatal screening, the ability to accurately diagnose Down syndrome (DS) is still limited and better diagnostic testing is needed. METHODS: Plasma from 8 women carrying a DS foetus and 12 with non-DS foetuses matched for gestational age, maternal age and ethnicity, in the second trimester of pregnancy, was analysed by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in order to identify biomarkers for DS. RESULTS: Gel comparison revealed nine proteins differentially expressed in maternal plasma in women with DS foetuses. Eight proteins, transthyretin (TTHY), ceruloplasmin (CERU), afamin (AFAM), alpha-1-microglobulin (AMBP), apolipoprotein E (APOE), serum amyloid P-component (SAMP), histidine-rich glycoprotein (HRG) and alpha-1-antitrypsin (A1AT) were up-regulated and one, clusterin (CLUS), down-regulated. All nine proteins are known to be involved in foetal growth and development. APOE, SAMP, AFAM and CLUS are associated with the DS phenotype. Western blot and densitometric analysis of APOE and SAMP confirmed the increase of both proteins by 19 and 48% respectively. CONCLUSIONS: All differentially expressed proteins are candidate biomarkers for DS, providing opportunities for the development of non-invasive prenatal diagnosis. As these are preliminary findings, follow-up experiments are needed for their evaluation. Copyright (c) 2008 John Wiley & Sons, Ltd.
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