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

被引：2

作者：

de Koning, Maayke A. ^{[2
]}

Pimienta Ramirez, Paula A. ^{[3
]}

Haak, Monique C. ^{[4
]}

Han, Xiao ^{[3
]}

Ruiterkamp-Versteeg, Martina H. A. ^{[5
]}

de Leeuw, Nicole ^{[5
]}

Schatz, Ulrich A. ^{[6
,7
]}

Shoukier, Moneef ^{[8
]}

Rieger-Fackeldey, Esther ^{[9
]}

Ortiz, Javier U. ^{[7
]}

van Duinen, Sjoerd G. ^{[10
]}

Klein, Willemijn M. ^{[11
]}

Witlox, Ruben S. G. M. ^{[12
]}

Finnell, Richard H. ^{[3
,13
]}

Santen, Gijs W. E. ^{[2
]}

Lei, Yunping ^{[3
]}

Suerink, Manon ^{[1
,2
]}

机构：

[1] Leiden Univ Med Ctr, Dept Clin Genet, NL-2333 ZA Leiden, Netherlands

[2] Leiden Univ Med Ctr, Dept Clin Genet, Leiden, Netherlands

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX USA

[4] Leiden Univ Med Ctr, Dept Obstet, Leiden, Netherlands

[5] Radboudumc, Dept Human Genet, Nijmegen, Netherlands

[6] Tech Univ Munich, Inst Human Genet, Munich, Germany

[7] Tech Univ Munich, Dept Obstet & Gynecol, Munich, Germany

[8] Prenatal Med Munich, Dept Mol Genet, Munich, Germany

[9] Tech Univ Munich, Dept Neonatol, Munich, Germany

[10] Leiden Univ Med Ctr, Dept Pathol, Leiden, Netherlands

[11] Radboudumc, Dept Med Imaging, Nijmegen, Netherlands

[12] Leiden Univ Med Ctr, Dept Neonatol, Leiden, Netherlands

[13] Baylor Coll Med, Dept Med Mol & Cellular Biol & Mol & Human Genet, Houston, TX USA

来源：

JOURNAL OF MEDICAL GENETICS | 2024年 / 61卷 / 06期

关键词：

Whole Exome Sequencing; Genetic Diseases; Inborn; Genetics; Medical; Human Genetics; Genetic Testing; POLARITY;

D O I：

10.1136/jmg-2023-109698

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：549 / 552

页数：4

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