Skip to main content
SpringerLink
Log in

Levels of Circulating mRNA for the Tenascin-X (TNXB) Gene in Maternal Plasma at the Second Trimester in Pregnancies with Isolated Congenital Ventricular Septal Defects

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Objective

Maternal plasma is a source of circulating placental nucleic acids. In this study, we validated previous observations on abnormal levels of circulating messenger RNA (mRNA) for the tenascin-X gene in pregnancies with ventricular septal defects in the second trimester of pregnancy.

Methods

This was a bicentric retrospective study conducted from March 2016 to July 2017. Real-time polymerase chain reaction was used to identify abnormally expressed genes, comparing ten women carrying a euploid fetus with ventricular septal defects to 30 controls at 19–24 weeks of gestation. The univariable analysis was used to determine whether the mean mRNA for the tenascin-X gene values would differ from the expected values for the controls.

Results

mRNA for tenascin-X gene values was higher in ventricular septal defects, 4.38 ± 3.01 versus 1.00 ± 0.80. The result was still significant even after adjustment for gestational age.

Conclusions

These data confirm previous studies on the specific association of mRNA species and type of congenital heart defect and confirm that ventricular septal defects are associated with abnormal mRNA for the tenascin-X gene. The positive predictive value of this molecular marker in the general population should be assessed through prospective studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bernier PL, Stefanescu A, Samoukovic G, Tchervenkov CI. The challenge of congenital heart disease worldwide: epidemiologic and demographic facts. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2010;13:26–34.

    Article  PubMed  Google Scholar 

  2. Jone PN, Schowengerdt KO. Prenatal diagnosis of congenital heart disease. Pediatr Clin N Am. 2009;56:709–15.

    Article  Google Scholar 

  3. Rasiah SV, Publicover M, Ewer AK, Khan KS, Kilby MD, Zamora J. A systematic review of the accuracy of first-trimester ultrasound examination for detecting major congenital heart disease. Ultrasound Obstet Gynecol. 2006;28:110–6.

    Article  CAS  PubMed  Google Scholar 

  4. Tegnander E, Eik-Nes SH. The examiner’s ultrasound experience has a significant impact on the detection rate of congenital heart defects at the second-trimester fetal examination. Ultrasound Obstet Gynecol. 2006;28:8–14.

    Article  CAS  PubMed  Google Scholar 

  5. Karadzov-Orlic N, Egic A, Filimonovic D, Damnjanovic-Pazin B, Milovanovic Z, Lukic R, Mandic V, Joksic I, Vukomanovic V, Kosutic J, Djuricic S, Mikovic Z. Screening performances of abnormal first-trimester ductus venosus blood flow and increased nuchal translucency thickness in detection of major heart defects. Prenat Diagn. 2015;35:1308–15.

    Article  PubMed  Google Scholar 

  6. Alanen J, Leskinen M, Sairanen M, Korpimaki T, Kouru H, Gissler M, Ryynanen M, Nevalainen J. Fetal nuchal translucency in severe congenital heart defects: experiences in Northern Finland. J Matern Fetal Neonatal Med. 2017;3:1–7.

    Article  Google Scholar 

  7. van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, Roos-Hesselink JW. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:2241–7.

    Article  PubMed  Google Scholar 

  8. Paladini D, Volpe P. Ultrasound of congenital fetal anomalies. London: Informa Healthcare; 2007.

    Book  Google Scholar 

  9. Sands AJ, Casey FA, Craig BG, Dornan JC, Rogers J, Mulholland HC. Incidence and risk factors for ventricular septal defect in “low risk” neonates. Arch Dis Child Fetal Neonatal Ed. 1999;81:F61–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Newman TB. Etiology of ventricular septal defects: an epidemiologic approach. Pediatrics. 1985;76:741–9.

    CAS  PubMed  Google Scholar 

  11. Auger N, Fraser WD, Healy-Profitós J, Arbour L. Association between preeclampsia and congenital heart defects. JAMA. 2015;314:1588–98.

    Article  CAS  PubMed  Google Scholar 

  12. Thilaganathan B. Preeclampsia and fetal congenital heart defects: spurious association or maternal confounding? Circulation. 2017;136:49–51.

    Article  PubMed  Google Scholar 

  13. Llurba E, Sánchez O, Ferrer Q, et al. Maternal and foetal angiogenic imbalance in congenital heart defects. Eur Heart J. 2014;35:701–7.

    Article  CAS  PubMed  Google Scholar 

  14. Sliwa K, Mebazaa A. Possible joint pathways of early pre-eclampsia and congenital heart defects via angiogenic imbalance and potential evidence for cardio-placental syndrome. Eur Heart J. 2014;35:680–2.

    Article  PubMed  Google Scholar 

  15. Arcelli D, Farina A, Cappuzzello C, Bresin A, De Sanctis P, Perolo A, Prandstraller D, Valentini D, Zucchini C, Priori S, Rizzo N. Identification of circulating placental mRNA in maternal blood of pregnancies affected with fetal congenital heart diseases at the second trimester of pregnancy: implications for early molecular screening. Prenat Diagn. 2010;30:229–34.

    CAS  PubMed  Google Scholar 

  16. Curti A, Lapucci C, Berto S, Prandstraller D, Perolo A, Rizzo N, Farina A. Maternal plasma mRNA species in fetal heart defects: a potential for molecular screening. Prenat Diagn. 2016;36:738–43.

    Article  CAS  PubMed  Google Scholar 

  17. Contro E, Stefani L, Berto S, Lapucci C, Arcelli D, Prandstraller D, Perolo A, Rizzo N, Farina A. Circulating mRNA in maternal plasma at the second trimester of pregnancy: a possible screening tool for cardiac conotruncal and left ventricular outflow tract abnormalities. Mol Diagn Ther. 2017;21:653–61.

    Article  CAS  PubMed  Google Scholar 

  18. Yu Z, Han S, Hu P, Zhu C, Wang X, Qian L, Guo X. Potential role of maternal serum microRNAs as a biomarker for fetal congenital heart defects. Med Hypotheses. 2011;76:424–6.

    Article  CAS  PubMed  Google Scholar 

  19. Zhu S, Cao L, Zhu J, Kong L, Jin J, Qian L, Zhu C, Hu X, Li M, Guo X, Han S, Yu Z. Identification of maternal serum microRNAs as novel non-invasive biomarkers for prenatal detection of fetal congenital heart defects. Clin Chim Acta. 2013;424:66–72.

    Article  CAS  PubMed  Google Scholar 

  20. Bornstein P, Sage E. Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol. 2002;14:608–16 [PubMed: 12231357].

    Article  CAS  PubMed  Google Scholar 

  21. Lincoln J, Alfieri CM, Yutzey KE. Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos. Dev Dyn. 2004;230:239–50.

    Article  CAS  PubMed  Google Scholar 

  22. Imanaka-Yoshida K, Matsumoto K, Hara M, Sakakura T, Yoshida T. The dynamic expression of tenascin-C and tenascin-X during early heart development in the mouse. Differentiation. 2003;71:291–8.

    Article  CAS  PubMed  Google Scholar 

  23. Combs MD, Yutzey KE. Heart valve development: regulatory networks in development and disease. Circ Res. 2009;105:408–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  25. Rothman KJ, Fyler DC. Seasonal occurrence of complex ventricular septal defect. Lancet. 1974;2:193–7.

    Article  CAS  PubMed  Google Scholar 

  26. Rosenberg LA, Heinonen OP. Seasonal occurrence of ventricular septal defect. Lancet. 1974;2:903–4.

    Article  CAS  PubMed  Google Scholar 

  27. Gu H, Li H, Zhang L, Luan H, Huang T, Wang L, Fan Y, Zhang Y, Liu X, Wang W, Yuan Z. Diagnostic role of microRNA expression profile in the serum of pregnant women with fetuses with neural tube defects. J Neurochem. 2012;122:641–9.

    Article  CAS  PubMed  Google Scholar 

  28. Li X, Zhao Z. MicroRNA biomarkers for early detection of embryonic malformations in pregnancy. J Biomol Res Ther. 2014;3:119.

    PubMed  PubMed Central  Google Scholar 

  29. Miura K, Miura S, Yamasaki K, Higashijima A, Kinoshita A, Yoshiura K, Masuzaki H. Identification of pregnancy-associated microRNAs in maternal plasma. Clin Chem. 2010;56:1767–71.

    Article  CAS  PubMed  Google Scholar 

  30. Petersen JW, Douglas JY. Tenascin-X, collagen, and Ehlers-Danlos syndrome: tenascin-X gene defects can protect against adverse cardiovascular events. Med Hypotheses. 2013;81:443–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Matsumoto K, Saga Y, Ikemura T, et al. The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C. J Cell Biol. 1994;125:483–93.

    Article  CAS  PubMed  Google Scholar 

  32. Zhou J, Zhang Y, Gui Y, Chu C, Zhang C, Zhou Q, Zhang Y, Li X, Yan Y. Relationship between isolated mild tricuspid valve regurgitation in second-trimester fetuses and postnatal congenital cardiac disorders. J Ultrasound Med. 2014;33:1677–82.

    Article  PubMed  Google Scholar 

  33. Mo FE, Lau LF. The matricellular protein CCN1 is essential for cardiac development. Circ Res. 2006;99:961–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Morphology, Surgery and Experimental Medicine, Section of Obstetrics and Gynecology, University of Ferrara, Azienda Ospedaliero-Universitaria S. Anna, Cona, Ferrara, Italy

    Danila Morano

  2. Genetic Unit, Synlab Italia, Brescia, Italy

    Silvia Berto, Cristina Lapucci & Lara Walczer Baldinazzo

  3. Pediatric Cardiology and Adult Congenital Unit, Sant’Orsola-Malpighi Hospital, Bologna, Italy

    Daniela Prandstraller

  4. Division of Obstetrics and Prenatal Medicine, Department of Medicine and Surgery (DIMEC), Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    Antonio Farina

Authors
  1. Danila Morano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvia Berto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristina Lapucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lara Walczer Baldinazzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniela Prandstraller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Farina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Farina.

Ethics declarations

Conflict of interest

D. Morano, S. Berto, C. Lapucci, L. Walczer Baldinazzo D. Prandstraller, and A. Farina declare that they have no conflict of interest.

Funding

This study was funded by RFO University of Bologna, Italy (A. Farina) and by Synlab Brescia (S. Berto and C. Lapucci).

Ethical approval and informed consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morano, D., Berto, S., Lapucci, C. et al. Levels of Circulating mRNA for the Tenascin-X (TNXB) Gene in Maternal Plasma at the Second Trimester in Pregnancies with Isolated Congenital Ventricular Septal Defects. Mol Diagn Ther 22, 235–240 (2018). https://doi.org/10.1007/s40291-018-0321-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-018-0321-4

Search

Navigation