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Maternal serum protein profile and immune response protein subunits as markers for non-invasive prenatal diagnosis of trisomy 21, 18, and 13

Authors

  • Kothandaraman Narasimhan,

    1. Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
    2. Centre for Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
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    • These authors contributed equally.
  • Su Lin Lin,

    1. Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
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  • Terry Tong,

    1. Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
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  • Sonia Baig,

    1. Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
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  • Sherry Ho,

    1. Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
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  • Ponnusamy Sukumar,

    1. Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
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  • Arijit Biswas,

    1. Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
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  • Sinuhe Hahn,

    1. Pränatale Medizin, Universitätsspital Basel, Basel, Switzerland
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  • Vladimir B. Bajic,

    1. King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center, Thuwal, Saudi Arabia
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    • These authors contributed equally.
  • Mahesh Choolani

    Corresponding author
    • Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, Singapore
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    • These authors contributed equally.

  • Funding sources: This work was supported by the National Medical Research Council (NMRC), Singapore (Grant number: R173-000-071-213) and the Biomedical Research Council (BMRC) Singapore (Grant number: R174-000-091-305) for providing funds to carry out this project.
  • Conflicts of interest: None declared.

Correspondence to: Mahesh Choolani. E-mail: obgmac@nus.edu.sg

ABSTRACT

Objectives

To use proteomics to identify and characterize proteins in maternal serum from patients at high-risk for fetal trisomy 21, trisomy 18, and trisomy 13 on the basis of ultrasound and maternal serum triple tests.

Methods

We performed a comprehensive proteomic analysis on 23 trisomy cases and 85 normal cases during the early second trimester of pregnancy. Protein profiling along with conventional sodium dodecyl sulfate polyacrylamide gel electrophoresis/Tandem mass spectrometry analysis was carried out to characterize proteins associated with each trisomy condition and later validated using Western blot.

Results

Protein profiling approach using surface enhanced laser desorption/ionization time-of-flight mass (SELDI-TOF/MS) spectrometry resulted in the identification of 37 unique hydrophobic proteomic features for three trisomy conditions. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by Matrix Assisted Laser Desorption Ionization – Time of Flight/Time of Flight (MALDI-TOF/TOF) and western blot, glyco proteins such as alpha-1-antitrypsin, apolipoprotein E, apolipoprotein H, and serum carrier protein transthyretin were identified as potential maternal serum markers for fetal trisomy condition. The identified proteins showed differential expression at the subunit level. .

Conclusions

Maternal serum protein profiling using proteomics may allow non-invasive diagnostic testing for the most common trisomies and may complement ultrasound-based methods to more accurately determine pregnancies with fetal aneuploidies. © 2013 John Wiley & Sons, Ltd.

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