Role ofﾠWNT10Aﾠin failure of tooth development in humans and zebrafish

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dc.citation.firstpage730en_US
dc.citation.issueNumber6en_US
dc.citation.journalTitleMolecular Genetics & Genomic Medicineen_US
dc.citation.lastpage741en_US
dc.citation.volumeNumber5en_US
dc.contributor.authorYuan, Qiupingen_US
dc.contributor.authorZhao, Minen_US
dc.contributor.authorTandon, Bhavnaen_US
dc.contributor.authorMaili, Lorenaen_US
dc.contributor.authorLiu, Xiaomingen_US
dc.contributor.authorZhang, Anqien_US
dc.contributor.authorBaugh, Evan H.en_US
dc.contributor.authorTran, Tamen_US
dc.contributor.authorSilva, Renato M.en_US
dc.contributor.authorHecht, Jacqueline T.en_US
dc.contributor.authorSwindell, Eric C.en_US
dc.contributor.authorWagner, Daniel S.en_US
dc.contributor.authorLetra, Ariadneen_US
dc.date.accessioned2018-07-11T17:18:37Zen_US
dc.date.available2018-07-11T17:18:37Zen_US
dc.date.issued2017en_US
dc.description.abstractBackground: Oligodontia is a severe form of tooth agenesis characterized by the absence of six or more permanent teeth. Oligodontia has complex etiology and variations in numerous genes have been suggested as causal for the condition. Methods: We applied whole‐exome sequencing (WES) to identify the cause of oligodontia in a 9‐year‐old girl missing 11 permanent teeth. Protein modeling and functional analysis in zebrafish were also performed to understand the impact of identified variants on the phenotype. Results: We identified a novel compound heterozygous missense mutation in WNT10A (c.637G>A:p.Gly213Ser and c.1070C>T:p.Thr357Ile) as the likely cause of autosomal recessive oligodontia in the child. Affected residues are located in conserved regions and variants are predicted to be highly deleterious for potentially destabilizing the protein fold and inhibiting normal protein function. Functional studies in zebrafish embryos showed that wnt10a is expressed in the craniofacies at critical time points for tooth development, and that perturbations of wnt10a expression impaired normal tooth development and arrested tooth development at 5 days postfertilization (dpf). Furthermore, mRNA expression levels of additional tooth development genes were directly correlated with wnt10a expression; expression of msx1, dlx2b, eda, and axin2 was decreased upon wnt10a knockdown, and increased upon wnt10a overexpression. Conclusions: Our results reveal a novel compound heterozygous variant in WNT10A as pathogenic for oligodontia, and demonstrate that perturbations of wnt10a expression in zebrafish may directly and/or indirectly affect tooth development recapitulating the agenesis phenotype observed in humans.en_US
dc.identifier.citationYuan, Qiuping, Zhao, Min, Tandon, Bhavna, et al.. "Role ofﾠWNT10Aﾠin failure of tooth development in humans and zebrafish." <i>Molecular Genetics & Genomic Medicine,</i> 5, no. 6 (2017) Wiley: 730-741. https://doi.org/10.1002/mgg3.332.en_US
dc.identifier.doihttps://doi.org/10.1002/mgg3.332en_US
dc.identifier.urihttps://hdl.handle.net/1911/102385en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleRole ofﾠWNT10Aﾠin failure of tooth development in humans and zebrafishen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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