Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin–twin transfusion syndrome

Authors

  • Lisa Hui,

    Corresponding author
    1. Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney, Sydney, New South Wales, Australia
    • Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA
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  • Heather C. Wick,

    1. Department of Computer Science, Tufts University, Medford, MA, USA
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  • Kenneth J. Moise Jr.,

    1. Department of Obstetrics, Gynecology and Reproductive Medicine, Division of Maternal–Fetal Medicine, University of Texas School of Medicine at Houston, Houston, TX, USA
    2. Texas Fetal Center, Children's Memorial Hermann Hospital, Houston, TX, USA
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  • Anthony Johnson,

    1. Department of Obstetrics, Gynecology and Reproductive Medicine, Division of Maternal–Fetal Medicine, University of Texas School of Medicine at Houston, Houston, TX, USA
    2. Texas Fetal Center, Children's Memorial Hermann Hospital, Houston, TX, USA
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  • Francois Luks,

    1. Warren Alpert Medical School and the Fetal Treatment Program of New England, Brown University, Providence, RI, USA
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  • Sina Haeri,

    1. Department of Obstetrics and Gynecology, Division of Maternal–Fetal Medicine, Baylor College of Medicine, Houston, TX, USA
    2. Texas Children's Fetal Center, Texas Children's Hospital, Houston, TX, USA
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  • Kirby L. Johnson,

    1. Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA
    2. Department of Computer Science, Tufts University, Medford, MA, USA
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  • Diana W. Bianchi

    1. Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA
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  • Funding sources: Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants R01 HD42053-09 and R01 HD058880; the University of Sydney Medical School (Albert S. McKern Research Scholarship to Dr Hui); and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (Fotheringham Fellowship to Dr Hui).

  • Conflicts of interest: None declared

Correspondence to: Lisa Hui. E-mail: lisahui77@gmail.com

ABSTRACT

Objective

The objective of this study was to understand the biological pathways involved in twin–twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA.

Methods

A prospective whole transcriptome microarray study analyzing cell-free RNA in AF from TTTS recipient twins and singleton controls was carried out. Significantly differentially regulated genes in TTTS cases (N = 8) versus matched controls (N = 8) were identified and pathways analyses performed. Significant gene expression differences between stage II TTTS recipients (N = 5) and stage III TTTS recipients with abnormal Doppler measurements (N = 5) were also analyzed.

Results

Analysis of paired data from TTTS cases and controls revealed differential expression of 801 genes, which were significantly enriched for neurological disease and cardiovascular system pathways. We also identified cardiovascular genes and pathways associated with the presence of critically abnormal Doppler measurements in stage III TTTS recipients.

Conclusions

This study provides the first transcriptome-wide data on the impact of TTTS on fetal development. Our results show that gene expression involving neurological and cardiovascular pathways are altered in recipient fetuses prior to surgical treatment. This has relevance for the origins of long-term complications seen in survivors and for the development of future fetal biomarkers. © 2013 John Wiley & Sons, Ltd.

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