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Bioinformatic and conformational analyses, fluorescence microscopy and luciferase reporter assay were employed to explore the functional impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified three novel variants in the\n                      <jats:italic>PAX9<\/jats:italic>\n                      , including two frameshift variants (c.211_212insA; p.I71Nfs*246 and c.236_237insAC; p.T80Lfs*6\n                      <jats:italic>)<\/jats:italic>\n                      , and one missense variant (c.229C\u00a0&gt;\u00a0G; p.R77G). Familial co\u2010segregation verified an autosomal\u2010dominant inheritance pattern. Conformational analyses revealed that the variants resided in the paired domain, and could cause corresponding structural impairment of the PAX9 protein. Fluorescence microscopy showed abnormal subcellular localizations of frameshift variants, and luciferase assay showed impaired downstream transactivation activities of the\n                      <jats:italic>bone morphogenetic protein 4<\/jats:italic>\n                      (\n                      <jats:italic>BMP4<\/jats:italic>\n                      ) gene in all variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings broaden the spectrum of\n                      <jats:italic>PAX9<\/jats:italic>\n                      variants in patients with non\u2010syndromic oligodontia and support that paired domain structural impairment and the dominant\u2010negative effect are likely the underlying mechanisms of\n                      <jats:italic>PAX9<\/jats:italic>\n                      \u2010related non\u2010syndromic oligodontia. Our findings will facilitate genetic diagnosis and counselling, and help lay the foundation for precise oral health therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.13684","type":"journal-article","created":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T04:45:03Z","timestamp":1603169103000},"page":"1468-1477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Functional study of novel\n                    <i>PAX9<\/i>\n                    variants: The paired domain and non\u2010syndromic oligodontia"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0552-970X","authenticated-orcid":false,"given":"Kai","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology and National Clinical Research Centre for Oral Diseases and National Engineering Laboratory 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