Identification of Novel CELSR1 Mutations in Spina Bifida

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dc.creatorLei, Yunpingen
dc.creatorZhu, Huipingen
dc.creatorYang, Weien
dc.creatorRoss, M. Elizabethen
dc.creatorShaw, Gary M.en
dc.creatorFinnell, Richard H.en
dc.date.accessioned2014-12-15T17:10:36Zen
dc.date.available2014-12-15T17:10:36Zen
dc.date.issued2014-03-14en
dc.descriptionYunping Lei, Huiping Zhu, Richard H. Finnell, Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas, United States of Americaen
dc.descriptionRichard H. Finnell, Department of Chemistry, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, United States of Americaen
dc.descriptionWei Yang, Gary M. Shaw, Department of Pediatrics, Division of Neonatology, Stanford University School of Medicine, Stanford, California, United States of Americaen
dc.descriptionM. Elizabeth Ross, Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, United States of Americaen
dc.description.abstractSpina bifida is one of the most common neural tube defects (NTDs) with a complex etiology. Variants in planar cell polarity (PCP) genes have been associated with NTDs including spina bifida in both animal models and human cohorts. In this study, we sequenced all exons of CELSR1 in 192 spina bifida patients from a California population to determine the contribution of CELSR1 mutations in the studied population. Novel and rare variants identified in these patients were subsequently genotyped in 190 ethnically matched control individuals. Six missense mutations not found in controls were predicted to be deleterious by both SIFT and PolyPhen. Two TG dinucleotide repeat variants were individually detected in 2 spina bifida patients but not detected in controls. In vitro functional analysis showed that the two TG dinucleotide repeat variants not only changed subcellular localization of the CELSR1 protein, but also impaired the physical association between CELSR1 and VANGL2, and thus diminished the ability to recruit VANGL2 for cell-cell contact. In total, 3% of our spina bifida patients carry deleterious or predicted to be deleterious CELSR1 mutations. Our findings suggest that CELSR1 mutations contribute to the risk of spina bifida in a cohort of spina bifida patients from California.en
dc.description.catalogingnoteEmail: rfinnell@austin.utexas.eduen
dc.description.departmentDell Pediatric Research Instituteen
dc.description.departmentNutritional Sciencesen
dc.description.departmentChemistryen
dc.description.sponsorshipThis work was supported in part by NIH grants HD067244, NS076465, and ES021006. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.Filenamejournal.pone.0092207.pdfen
dc.identifier.citationLei Y, Zhu H, Yang W, Ross ME, Shaw GM, et al. (2014) Identification of Novel CELSR1 Mutations in Spina Bifida. PLoS ONE 9(3): e92207. doi:10.1371/journal.pone.0092207en
dc.identifier.doiDOI: 10.1371/journal.pone.0092207en
dc.identifier.urihttp://hdl.handle.net/2152/27904en
dc.language.isoEnglishen
dc.publisherPLOS Oneen
dc.rightsAdministrative deposit of works to UT Digital Repository: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access at http://www.plosone.org. The public license is specified as CC-BY: http://creativecommons.org/licenses/by/4.0/. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en
dc.subjectCaliforniaen
dc.subjectcell membranesen
dc.subjectdamage mechanicsen
dc.subjectdinucleotide repeatsen
dc.subjectinfantsen
dc.subjectmutationen
dc.subjectpneumocystisen
dc.subjectspina bifidaen
dc.titleIdentification of Novel CELSR1 Mutations in Spina Bifidaen
dc.typeArticleen

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