{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:58:35Z","timestamp":1767837515978,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20313"],"award-info":[{"award-number":["U22A20313"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970904"],"award-info":[{"award-number":["81970904"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tooth agenesis (TA) ranks among the most common dental abnormalities. This study aimed to explore the etiology and pathogenesis in Chinese families with non\u2010syndromic TA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Chinese families exhibiting non\u2010syndromic TA were recruited. Exome sequencing was conducted to identify mutations in the candidate genes, followed by Sanger sequencing for validation. Functional studies, including bioinformatics analyses, western blots, and dual\u2010luciferase assays, were performed to analyze the impact of the two mutations on the Wnt\/\u03b2\u2010catenin pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel heterozygous frameshift insertion in <jats:italic>AXIN2<\/jats:italic> [NM_001363813.1: c.1799dupG (p.Asn601GlnfsTer41)] and a novel <jats:italic>de novo<\/jats:italic> heterozygous non\u2010frameshift deletion in <jats:italic>LRP6<\/jats:italic> [NM_002336.3: c.3074_3082del (p.1025_1028del)]. Further functional studies indicated that AXIN2 p.Asn601GlnfsTer41 caused hyperactivation of the Wnt\/\u03b2\u2010catenin pathway, and LRP6 p.1025_1028del led to pathway suppression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study expands the spectrum of <jats:italic>AXIN2<\/jats:italic> and <jats:italic>LRP6<\/jats:italic> mutations associated with non\u2010syndromic TA. Our study provided further functional evidence supporting the pathogenicity of suppression and excessive activation of the Wnt signaling pathway in TA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70101","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T11:24:34Z","timestamp":1745839474000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification and Functional Analysis of Novel Mutations in <i>AXIN2<\/i> and <i>LRP6<\/i> Linked With Non\u2010Syndromic Tooth Agenesis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4031-6391","authenticated-orcid":false,"given":"Wendi","family":"Luo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitang","family":"Yue","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; 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