Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects

Ciprian M Bosoi; Valeria Capra; Redouane Allache; Vincent Quoc-Huy Trinh; Patrizia De Marco; Elisa Merello; Pierre Drapeau; Alexander G Bassuk; Zoha Kibar

doi:10.1002/humu.21589

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Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects

Journal article

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Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects

Ciprian M Bosoi, Valeria Capra, Redouane Allache, Vincent Quoc-Huy Trinh, Patrizia De Marco, Elisa Merello, Pierre Drapeau, Alexander G Bassuk and Zoha Kibar

Human mutation, Vol.32(12), pp.1371-1375

12/2011

DOI: 10.1002/humu.21589

PMCID: PMC3217084

PMID: 21901791

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Abstract

The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure and has been implicated in the pathogenesis of neural tube defects (NTDs) in animal models and human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1 in these malformations. We screened this gene in 810 unrelated NTD patients and identified 7 rare missense heterozygous mutations that were absent in all controls analyzed and predicted to be functionally deleterious using bioinformatics. Functional validation of 5 PRICKLE1 variants in a zebrafish model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a in a dominant fashion. Our study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs and further expands our knowledge of the role of PCP genes in the pathogenesis of these malformations.

Planar cell polarity

neural tube defects

PRICKLE1

rare mutations

PCP

NTD

Details

Title: Subtitle: Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects
Creators: Ciprian M Bosoi - Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montréal
Valeria Capra - Laboratorio del Servizio di Neurochirurgia, Instituto G. Gaslini, Genova, Italy
Redouane Allache - Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montréal
Vincent Quoc-Huy Trinh - Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montréal
Patrizia De Marco - Laboratorio del Servizio di Neurochirurgia, Instituto G. Gaslini, Genova, Italy
Elisa Merello - Laboratorio del Servizio di Neurochirurgia, Instituto G. Gaslini, Genova, Italy
Pierre Drapeau - Department of Pathology and Cell Biology, University of Montreal, Montreal, Canada
Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Zoha Kibar - Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montréal
Resource Type: Journal article
Publication Details: Human mutation, Vol.32(12), pp.1371-1375
DOI: 10.1002/humu.21589
PMID: 21901791
PMCID: PMC3217084
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Grant note: R01 NS064159-02 || NS / National Institute of Neurological Disorders and Stroke : NINDS
Language: English
Date published: 12/2011
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984013201802771

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