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Human Genetics

, Volume 133, Issue 9, pp 1075–1082 | Cite as

Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome

  • Lauren J. MassinghamEmail author
  • Kirby L. Johnson
  • Thomas M. Scholl
  • Donna K. Slonim
  • Heather C. Wick
  • Diana W. Bianchi
Original Investigation

Abstract

Turner syndrome is a sex chromosome aneuploidy with characteristic malformations. Amniotic fluid, a complex biological material, could contribute to the understanding of Turner syndrome pathogenesis. In this pilot study, global gene expression analysis of cell-free RNA in amniotic fluid supernatant was utilized to identify specific genes/organ systems that may play a role in Turner syndrome pathophysiology. Cell-free RNA from amniotic fluid of five mid-trimester Turner syndrome fetuses and five euploid female fetuses matched for gestational age was extracted, amplified, and hybridized onto Affymetrix® U133 Plus 2.0 arrays. Significantly differentially regulated genes were identified using paired t tests. Biological interpretation was performed using Ingenuity Pathway Analysis and BioGPS gene expression atlas. There were 470 statistically significantly differentially expressed genes identified. They were widely distributed across the genome. XIST was significantly down-regulated (p < 0.0001); SHOX was not differentially expressed. One of the most highly represented organ systems was the hematologic/immune system, distinguishing the Turner syndrome transcriptome from other aneuploidies we previously studied. Manual curation of the differentially expressed gene list identified genes of possible pathologic significance, including NFATC3, IGFBP5, and LDLR. Transcriptomic differences in the amniotic fluid of Turner syndrome fetuses are due to genome-wide dysregulation. The hematologic/immune system differences may play a role in early-onset autoimmune dysfunction. Other genes identified with possible pathologic significance are associated with cardiac and skeletal systems, which are known to be affected in females with Turner syndrome. The discovery-driven approach described here may be useful in elucidating novel mechanisms of disease in Turner syndrome.

Keywords

Amniotic Fluid Ingenuity Pathway Analysis Turner Syndrome Amniotic Fluid Sample Ingenuity Pathway Analysis Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Funding for this study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01 HD42053-10 to DWB and R01 HD058880-04 to DKS].

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

439_2014_1448_MOESM1_ESM.xls (88 kb)
Differentially up-regulated Turner syndrome gene list. (XLS 87 kb)
439_2014_1448_MOESM2_ESM.xls (70 kb)
Differentially down-regulated Turner syndrome gene list. (XLS 69 kb)
439_2014_1448_MOESM3_ESM.xls (18 kb)
Chi square analysis of gene dysregulation distribution. (XLS 18 kb)
439_2014_1448_MOESM4_ESM.xls (38 kb)
Turner syndrome transcriptome organ-specific genes identified by BioGPS. (XLS 38 kb)
439_2014_1448_MOESM5_ESM.xls (37 kb)
Turner syndrome transcriptome top biological functions identified by IPA. (XLS 37 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Lauren J. Massingham
    • 1
    Email author
  • Kirby L. Johnson
    • 2
  • Thomas M. Scholl
    • 3
  • Donna K. Slonim
    • 2
    • 4
  • Heather C. Wick
    • 4
  • Diana W. Bianchi
    • 1
  1. 1.Mother Infant Research Institute and Department of PediatricsFloating Hospital for Children at Tufts Medical CenterBostonUSA
  2. 2.Tufts University School of MedicineBostonUSA
  3. 3.Integrated Genetics, Esoterix Genetic LaboratoriesLLC, A Subsidiary of Laboratory Corporation of America® HoldingsWestboroughUSA
  4. 4.Department of Computer ScienceTufts UniversityMedfordUSA

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