You are here

Article Text

Article menu
Download PDFPDF
Genotype-phenotype correlations
Short report
De novo heterozygous missense variants in CELSR1 as cause of fetal pleural effusions and progressive fetal hydrops
  1. Maayke A de Koning1,
  2. Paula A Pimienta Ramirez2,
  3. Monique C Haak3,
  4. Xiao Han2,
  5. Martina HA Ruiterkamp-Versteeg4,
  6. Nicole de Leeuw4,
  7. Ulrich A Schatz5,6,
  8. Moneef Shoukier7,
  9. Esther Rieger-Fackeldey8,
  10. Javier U Ortiz6,
  11. Sjoerd G van Duinen9,
  12. Willemijn M Klein10,
  13. Ruben S G M Witlox11,
  14. Richard H Finnell2,12,
  15. Gijs W E Santen1,
  16. Yunping Lei2,
  17. Manon Suerink1
  1. 1 Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
  3. 3 Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands
  4. 4 Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands
  5. 5 Institute of Human Genetics, Technische Universität München, Munich, Germany
  6. 6 Department of Obstetrics and Gynecology, Technische Universität München, Munich, Germany
  7. 7 Department of Molecular Genetics, Prenatal Medicine Munich, Munich, Germany
  8. 8 Department of Neonatology, Technische Universität München, Munich, Germany
  9. 9 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
  10. 10 Department of Medical Imaging, Radboudumc, Nijmegen, The Netherlands
  11. 11 Department of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
  12. 12 Departments of Medicine, Molecular and Cellular Biology and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to Dr. Manon Suerink, Department of Clinical Genetics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands; m.suerink{at}lumc.nl

Abstract

Fetal hydrops as detected by prenatal ultrasound usually carries a poor prognosis depending on the underlying aetiology. We describe the prenatal and postnatal clinical course of two unrelated female probands in whom de novo heterozygous missense variants in the planar cell polarity gene CELSR1 were detected using exome sequencing. Using several in vitro assays, we show that the CELSR1 p.(Cys1318Tyr) variant disrupted the subcellular localisation, affected cell-cell junction, impaired planar cell polarity signalling and lowered proliferation rate. These observations suggest that deleterious rare CELSR1 variants could be a possible cause of fetal hydrops.

  • Whole Exome Sequencing
  • Genetic Diseases, Inborn
  • Genetics, Medical
  • Human Genetics
  • Genetic Testing

https://doi.org/10.1136/jmg-2023-109698

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • MAdK and PAPR are joint first authors.

    • YL and MS are joint senior authors.

    • YL and MS contributed equally.

    • Correction notice This article has been corrected since it was published online first. The corresponding author's email address was incorrectly duplicated; this has been corrected.

    • Contributors Conceptualisation: GWES and YL. Data curation: MdK and PAPR. Supervision: MS and YL. Writing original draft: MdK and PAPR. Writing—review and editing: All authors.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.