Frazier-Bowers Sylvia A, Puranik Chaitanya P, Mahaney Michael C
Department of Orthodontics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, Tel: (919) 966-2762, ,
Semin Orthod. 2010 Sep 1;16(3):180-185. doi: 10.1053/j.sodo.2010.05.003.
The clinical spectrum of tooth eruption disorders includes both syndromic and non-syndromic problems ranging from delayed eruption to a complete failure of eruption. A defect in the differential apposition/resorption mechanism in alveolar bone can cause conditions such as tooth ankylosis, primary failure of eruption, failure of eruption due to inadequate arch length and canine impaction. As our knowledge of the molecular events underlying normal tooth eruption has increased, so too has our understanding of clinical eruption disorders. The recent finding that one gene, parathyroid hormone receptor 1 (PTH1R), is causative for familial cases of primary failure of eruption (PFE) suggests that other disturbances in tooth eruption may have a genetic etiology. In this report, we evaluated the current terminology (ankylosis, PFE, secondary retention, etc.) used to describe non-syndromic eruption disorders, in light of this genetic discovery. We observed that some individuals previously diagnosed with ankylosis were subsequently found to have alterations in the PTH1R gene, indicating the initial misdiagnosis of ankylosis and the necessary re-classification of PFE. We further investigated the relationship of the PTH1R gene, using a network pathway analysis, to determine its connectivity to previously identified genes that are critical to normal tooth eruption. We found that PTH1R acts in a pathway with genes such as PTHrP that have been shown to be important in bone remodeling, hence eruption, in a rat model. Thus, recent advances in our understanding of normal and abnormal tooth eruption should allow us in the future to develop a clinical nomenclature system based more on the molecular genetic cause of the eruption failures versus the clinical appearance of the various eruption disorders.
牙齿萌出障碍的临床谱包括综合征性和非综合征性问题，范围从萌出延迟到完全萌出失败。牙槽骨中差异性附着/吸收机制的缺陷可导致诸如牙齿粘连、原发性萌出失败、由于牙弓长度不足导致的萌出失败以及尖牙阻生等情况。随着我们对正常牙齿萌出所涉及分子事件的了解不断增加，我们对临床萌出障碍的认识也在提高。最近发现甲状旁腺激素受体1（PTH1R）基因是家族性原发性萌出失败（PFE）病例的病因，这表明牙齿萌出的其他紊乱可能具有遗传病因。在本报告中，鉴于这一遗传学发现，我们评估了用于描述非综合征性萌出障碍的当前术语（粘连、PFE、继发性滞留等）。我们观察到，一些先前被诊断为粘连的个体随后被发现PTH1R基因存在改变，这表明最初对粘连的误诊以及对PFE进行必要的重新分类。我们使用网络通路分析进一步研究了PTH1R基因的关系，以确定其与先前确定的对正常牙齿萌出至关重要的基因的连接性。我们发现PTH1R在一条通路中与诸如PTHrP等基因共同作用，在大鼠模型中，这些基因已被证明在骨重塑以及因此在萌出过程中很重要。因此，我们对正常和异常牙齿萌出理解的最新进展应使我们未来能够开发一种临床命名系统，该系统更多地基于萌出失败的分子遗传原因而非各种萌出障碍的临床表现。
