Center of Excellence in Medical Genetics Research, Chiang Mai University, Chiang Mai, Thailand; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
School of Chemistry, Institute of Science, and Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima, Thailand.
Arch Oral Biol. 2022 Oct;142:105514. doi: 10.1016/j.archoralbio.2022.105514. Epub 2022 Jul 30.
The objective of this study was to investigate molecular etiologies of oral exostoses and dental anomalies in 14 patients from eight families.
Oral and radiographic examinations were performed on every patient. Whole exome and Sanger sequencing were performed on DNA of the patients, the unaffected parents and unaffected siblings. LRP6 mutant proteins were modeled and analyzed.
Five mutations in LRP6, including four missense (p.Glu72Lys, p.Lys82Asn, Tyr418His, and p.Ile773Val) and one nonsense mutation (p.Arg32Ter), were identified. These mutations have not been reported to be associated with dental anomalies or oral exostoses. Oral features included a variety of oral exostoses (7 of the 14 patients), root defects (6 of the 14 patients), and tooth agenesis (5 of the 14 patients). Less common dental anomalies included microdontia, tooth fusion, odontomas, and mesiodens. Analysis of the protein models of the five LRP6 mutations shed light on their likely impact on LRP6 protein structure and function.
Fourteen patients with five LRP6 mutations, including two recurrent mutations and three novel ones, are reported. Our study shows for the first time that mutations in LRP6 are associated with mesiodens, fusion of teeth, odontomas, microdontia, long roots, molars with unseparated roots, and taurodontism.
本研究旨在调查 8 个家系的 14 名患者口腔外生骨瘤和牙齿异常的分子病因。
对每位患者进行口腔和影像学检查。对患者、未受影响的父母和未受影响的兄弟姐妹的 DNA 进行全外显子组和 Sanger 测序。对 LRP6 突变蛋白进行建模和分析。
在 LRP6 中发现了 5 个突变，包括 4 个错义突变（p.Glu72Lys、p.Lys82Asn、Tyr418His 和 p.Ile773Val）和 1 个无义突变（p.Arg32Ter），这些突变与牙齿异常或口腔外生骨瘤无关。口腔特征包括多种口腔外生骨瘤（14 名患者中的 7 名）、根缺陷（14 名患者中的 6 名）和牙齿缺失（14 名患者中的 5 名）。不太常见的牙齿异常包括牙小、牙融合、牙瘤和中切牙。对这 5 个 LRP6 突变的蛋白模型分析揭示了它们对 LRP6 蛋白结构和功能的可能影响。
报告了 14 名患者存在 5 个 LRP6 突变，包括 2 个重复突变和 3 个新突变。我们的研究首次表明，LRP6 突变与中切牙、牙齿融合、牙瘤、牙小、根长、根未分离的磨牙和尖牙畸形有关。
