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There are numerous genotype\u2010phenotype publications involving many patients and kindreds. Here, we identified six Thai individuals in two families with nonsyndromic tooth agenesis, performed exome sequencing, and conducted functional experiments. Family 1 had four affected members carrying the heterozygous <jats:italic>PAX9<\/jats:italic> variant, c.59C&gt;T (p.Pro20Leu). The p.Pro20Leu was previously reported in two families having four and three affected members. These seven cases and Proband\u20101 had agenesis of at least three third molars. Family 2 comprised two affected members with agenesis of all 12 molars. Both individuals were heterozygous for c.230G&gt;A (p.Arg77Gln) in <jats:italic>PAX9<\/jats:italic>, which has not been reported previously. This variant is predicted to be damaging, evolutionarily conserved, and resides in the PAX9 linking peptide. The <jats:italic>BMP4<\/jats:italic> RNA levels in Proband\u20101\u2032s leukocytes were not significantly different from those in the controls, whereas <jats:italic>BMP4<\/jats:italic> levels observed in Proband\u20102 were significantly increased. Moreover, the p.Arg77Gln variant demonstrated nuclear localization similar to the wild\u2010type but resulted in significantly impaired transactivation of <jats:italic>BMP4<\/jats:italic>, a <jats:italic>PAX9<\/jats:italic> downstream gene. In conclusion, we demonstrate that the <jats:italic>PAX9<\/jats:italic> p.Pro20Leu is highly associated with absent third molars, while the novel <jats:italic>PAX9<\/jats:italic> p.Arg77Gln impairs <jats:italic>BMP4<\/jats:italic> transactivation and is associated with total molar agenesis.<\/jats:p>","DOI":"10.1111\/eos.12855","type":"journal-article","created":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T17:00:20Z","timestamp":1645290020000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Patterns of molar agenesis associated with p.P20L and p.R77Q variants in <i>PAX9<\/i>"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7504-1403","authenticated-orcid":false,"given":"Narin","family":"Intarak","sequence":"first","affiliation":[{"name":"Genomics and Precision Dentistry Research Unit Department of Physiology Faculty of Dentistry Chulalongkorn University  Bangkok 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