目的:本研究的目的是调查来自8个家庭的14例口腔外生骨和牙齿异常的分子病因。
方法:对每位患者进行口腔和影像学检查。对患者的DNA进行全外显子组和Sanger测序,未受影响的父母和未受影响的兄弟姐妹。对LRP6突变蛋白进行建模和分析。
结果:LRP6中的五个突变,包括四个错义(p。Glu72Lys,p.Lys82Asn,Tyr418His,和p.Ile773Val)和一个无义突变(p。Arg32Ter),已确定。尚未报道这些突变与牙齿异常或口腔外生骨有关。口腔特征包括各种口腔外生骨瘤(14例患者中有7例),根缺(14例患者中的6例),和牙齿发育不全(14例患者中有5例)。不太常见的牙齿异常包括微小牙体,牙齿融合,牙列切除术,还有mesiodens.五个LRP6突变的蛋白质模型的分析揭示了它们对LRP6蛋白质结构和功能的可能影响。
结论:14例患者有5个LRP6突变,包括两个复发突变和三个新突变,已报告。我们的研究首次表明LRP6的突变与mesiodens相关,牙齿融合,牙列切除术,microdontia,长根,有未分离的根的磨牙,和牛磺酸症。
OBJECTIVE: The objective of this study was to investigate molecular etiologies of oral exostoses and dental anomalies in 14 patients from eight families.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.