Detection of down syndrome by proteomic profiling of maternal serum


      To identify sensitive and specific protein profiles in maternal serum for the prenatal detection of Down syndrome in the 1st and 2nd trimesters.

      Study design

      Maternal sera from 50 patients (25 in the 2nd trimester and 25 in the 1st trimester, range 11–20 weeks) with Down's affected pregnancies were matched for gestational age and fetal sex with maternal sera from 50 unaffected pregnancies. Proteomic profiling was performed on unblinded maternal sera by fluorescent 2-dimensional gel electrophoresis and MALDI-TOF mass spectrometry.


      Proteomic profiling identified the differential expression of 6 proteins in Down's affected pregnancies that were differentially expressed in both the 1st and 2nd trimester. A proteomic profile utilizing these differentially expressed proteins correctly identified all 50 cases of Down syndrome, and in all cases distinguished them from unaffected controls in the matched pair samples. No control had a proteomic profile suggestive of Down syndrome. The presence of the differential protein expression between cases and controls in both 1st and 2nd trimester cases indicates the presence of common markers for Down syndrome across a broad range of gestational ages.


      Differential expression of proteins in maternal serum detected by proteomic profiling detected Down syndrome with 100% sensitivity and specificity in both 1st and 2nd trimester unblinded specimens.
      Supported by NIH 1U24DK5860, HD 38652, and by ProteoGenix, Inc.