{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T23:00:19Z","timestamp":1774393219110,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600846"],"award-info":[{"award-number":["81600846"]}],"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":["81970902"],"award-info":[{"award-number":["81970902"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the mutations in patients with Axenfeld\u2013Rieger syndrome (ARS) and the pattern of <jats:italic>PITX2<\/jats:italic>\u2010related tooth agenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing (WES) and copy number variation (CNV) array were used to screen the mutations in four ARS probands. After Sanger sequencing and quantitative polymerase chain reaction (qPCR) validation, secondary structure prediction and dual\u2010luciferase assay were employed to investigate the functional impact. Eighteen <jats:italic>PITX2<\/jats:italic>\u2010mutated patients with definite dental records were retrieved from our database and literatures, and the pattern of <jats:italic>PITX2<\/jats:italic>\u2010related tooth agenesis was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel de novo segmental deletion of chromosome 4q25 (GRCh37\/hg19 chr4:111, 320, 052\u2013111, 754, 236) encompassing <jats:italic>PITX2<\/jats:italic> and three novel <jats:italic>PITX2<\/jats:italic> mutations c.148C\u00a0&gt;\u00a0T, c.257G\u00a0&gt;\u00a0A, and c.630insCG were identified. Preliminary functional studies indicated the transactivation capacity of mutant PITX2 on <jats:italic>Distal\u2010less homeobox 2<\/jats:italic> (<jats:italic>DLX2<\/jats:italic>) promoter was compromised. The maxillary teeth showed significantly higher rate of agenesis (57.94%) than the mandibular teeth (44.05%). The most often missing teeth were upper lateral incisors (83.33%) and upper second premolars (69.44%). Teeth with the least agenesis rate were the lower second molars (19.44%) and lower first molars (8.33%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified a novel 4q25 microdeletion including <jats:italic>PITX2<\/jats:italic> and three novel <jats:italic>PITX2<\/jats:italic> mutations, and statistically analyzed the <jats:italic>PITX2<\/jats:italic>\u2010related tooth agenesis pattern.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.13196","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T05:25:00Z","timestamp":1568697900000},"page":"2010-2019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Novel <i>PITX2<\/i> mutations identified in Axenfeld\u2013Rieger syndrome and the pattern of <i>PITX2<\/i>\u2010related tooth 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