De novo heterozygous missense variants in <i>CELSR1</i> as cause of fetal pleural effusions and progressive fetal hydrops.

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 <i>de novo</i> heterozygous missense variants in the planar cell polarity gene <i>CELSR1</i> were detected using exome sequencing. Using several in vitro assays, we show that the <i>CELSR1</i> 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 <i>CELSR1</i> variants could be a possible cause of fetal hydrops.