{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T08:20:33Z","timestamp":1781857233821,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T00:00:00Z","timestamp":1505347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE011931"],"award-info":[{"award-number":["R01DE011931"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03DE024596"],"award-info":[{"award-number":["R03DE024596"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We applied whole\u2010exome sequencing (<jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content>) to identify the cause of oligodontia in a 9\u2010year\u2010old 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel compound heterozygous missense mutation in <jats:italic><jats:styled-content style=\"fixed-case\">WNT<\/jats:styled-content>10A<\/jats:italic> (c.637G&gt;A:p.Gly213Ser and c.1070C&gt;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 <jats:italic>wnt10a<\/jats:italic> is expressed in the craniofacies at critical time points for tooth development, and that perturbations of <jats:italic>wnt10a<\/jats:italic> expression impaired normal tooth development and arrested tooth development at 5\u00a0days postfertilization (dpf). Furthermore, <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression levels of additional tooth development genes were directly correlated with <jats:italic>wnt10a<\/jats:italic> expression; expression of <jats:italic>msx1, dlx2b, eda,<\/jats:italic> and <jats:italic>axin2<\/jats:italic> was decreased upon <jats:italic>wnt10a<\/jats:italic> knockdown, and increased upon <jats:italic>wnt10a<\/jats:italic> overexpression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results reveal a novel compound heterozygous variant in <jats:italic><jats:styled-content style=\"fixed-case\">WNT<\/jats:styled-content>10A<\/jats:italic> as pathogenic for oligodontia, and demonstrate that perturbations of <jats:italic>wnt10a<\/jats:italic> expression in zebrafish may directly and\/or indirectly affect tooth development recapitulating the agenesis phenotype observed in humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.332","type":"journal-article","created":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T07:29:44Z","timestamp":1505374184000},"page":"730-741","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Role of <i><scp>WNT<\/scp>10A<\/i> in failure of tooth development in humans and zebrafish"],"prefix":"10.1002","volume":"5","author":[{"given":"Qiuping","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Texas Health Science Center at Houston Medical School Houston Texas"},{"name":"Pediatric Research Center University of Texas Health Science Center at Houston Medical School Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Research University of Texas Health Science Center at Houston School of Dentistry 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