Article Text
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
Statistics from Altmetric.com
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.