De novo heterozygous missense variants in CELSR1 as cause of fetal pleural effusions and progressive fetal hydrops

Koning, M.A. de; Ramirez, P.A.P.; Haak, M.C.; Han, X.; Ruiterkamp-Versteeg, M.H.; Leeuw, N. de; ... ; Suerink, M. (2024)

Article / Letter to editor

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

• All authors: Koning, M.A. de; Ramirez, P.A.P.; Haak, M.C.; Han, X.; Ruiterkamp-Versteeg, M.H.; Leeuw, N. de; Schatz, U.A.; Shoukier, M.; Rieger-Fackeldey, E.; Ortiz, J.U.; Duinen, S.G. van; Klein, W.M.; Witlox, R.S.G.M.; Finnell, R.H.; Santen, G.W.E.; Lei, Y.P.; Suerink, M.
• Date: 2024-01-25
• Journal: Journal of Medical Genetics
• DOI: doi:10.1136/jmg-2023-109698