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

Maayke A. De Koning; Paula A. Pimienta Ramirez; Monique C. Haak; Xiao Han; Martina H.A. Ruiterkamp-Versteeg; Nicole De Leeuw; Ulrich A. Schatz; Moneef Shoukier; Esther Rieger-Fackeldey; Javier U. Ortiz; Sjoerd G. Van Duinen; Willemijn M. Klein; Ruben S.G.M. Witlox; Richard H. Finnell; Gijs W.E. Santen; Yunping Lei; Manon Suerink

doi:10.1136/jmg-2023-109698

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

Maayke A. De Koning, Paula A. Pimienta Ramirez, Monique C. Haak, Xiao Han, Martina H.A. Ruiterkamp-Versteeg, Nicole De Leeuw, Ulrich A. Schatz, Moneef Shoukier, Esther Rieger-Fackeldey, Javier U. Ortiz, Sjoerd G. Van Duinen, Willemijn M. Klein, Ruben S.G.M. Witlox, Richard H. Finnell, Gijs W.E. Santen, Yunping Lei, Manon Suerink

Department of Pediatric Medicine

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English
Pages (from-to)	549-552
Number of pages	4
Journal	Journal of Medical Genetics
Volume	61
Issue number	6
DOIs	https://doi.org/10.1136/jmg-2023-109698
State	Published - 1 Jun 2024

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/jmg-2023-109698

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De Koning, M. A., Pimienta Ramirez, P. A., Haak, M. C., Han, X., Ruiterkamp-Versteeg, M. H. A., De Leeuw, N., Schatz, U. A., Shoukier, M., Rieger-Fackeldey, E., Ortiz, J. U., Van Duinen, S. G., Klein, W. M., Witlox, R. S. G. M., Finnell, R. H., Santen, G. W. E., Lei, Y., & Suerink, M. (2024). De novo heterozygous missense variants in CELSR1 as cause of fetal pleural effusions and progressive fetal hydrops. Journal of Medical Genetics, 61(6), 549-552. https://doi.org/10.1136/jmg-2023-109698

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title = "De novo heterozygous missense variants in CELSR1 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 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.",

keywords = "Genetic Diseases, Inborn, Genetic Testing, Genetics, Medical, Human Genetics, Whole Exome Sequencing",

author = "{De Koning}, {Maayke A.} and {Pimienta Ramirez}, {Paula A.} and Haak, {Monique C.} and Xiao Han and Ruiterkamp-Versteeg, {Martina H.A.} and {De Leeuw}, Nicole and Schatz, {Ulrich A.} and Moneef Shoukier and Esther Rieger-Fackeldey and Ortiz, {Javier U.} and {Van Duinen}, {Sjoerd G.} and Klein, {Willemijn M.} and Witlox, {Ruben S.G.M.} and Finnell, {Richard H.} and Santen, {Gijs W.E.} and Yunping Lei and Manon Suerink",

year = "2024",

month = jun,

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doi = "10.1136/jmg-2023-109698",

language = "English",

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De Koning, MA, Pimienta Ramirez, PA, Haak, MC, Han, X, Ruiterkamp-Versteeg, MHA, De Leeuw, N, Schatz, UA, Shoukier, M, Rieger-Fackeldey, E, Ortiz, JU, Van Duinen, SG, Klein, WM, Witlox, RSGM, Finnell, RH, Santen, GWE, Lei, Y & Suerink, M 2024, 'De novo heterozygous missense variants in CELSR1 as cause of fetal pleural effusions and progressive fetal hydrops', Journal of Medical Genetics, vol. 61, no. 6, pp. 549-552. https://doi.org/10.1136/jmg-2023-109698

TY - JOUR

T1 - De novo heterozygous missense variants in CELSR1 as cause of fetal pleural effusions and progressive fetal hydrops

AU - De Koning, Maayke A.

AU - Pimienta Ramirez, Paula A.

AU - Haak, Monique C.

AU - Han, Xiao

AU - Ruiterkamp-Versteeg, Martina H.A.

AU - De Leeuw, Nicole

AU - Schatz, Ulrich A.

AU - Shoukier, Moneef

AU - Rieger-Fackeldey, Esther

AU - Ortiz, Javier U.

AU - Van Duinen, Sjoerd G.

AU - Klein, Willemijn M.

AU - Witlox, Ruben S.G.M.

AU - Finnell, Richard H.

AU - Santen, Gijs W.E.

AU - Lei, Yunping

AU - Suerink, Manon

PY - 2024/6/1

Y1 - 2024/6/1

N2 - 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.

AB - 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.

KW - Genetic Diseases, Inborn

KW - Genetic Testing

KW - Genetics, Medical

KW - Human Genetics

KW - Whole Exome Sequencing

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U2 - 10.1136/jmg-2023-109698

DO - 10.1136/jmg-2023-109698

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C2 - 38272662

AN - SCOPUS:85183871292

SN - 0022-2593

VL - 61

SP - 549

EP - 552

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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