School of Dentistry, Università Cattolica del Sacro Cuore, L.go Agostino Gemelli 8, 00168, Rome, Italy.
Fondazione Policlinico Universitario "A. Gemelli" IRCCS, L.go Agostino Gemelli 8, 00168, Rome, Italy.
Prog Orthod. 2021 Dec 13;22(1):43. doi: 10.1186/s40510-021-00387-z.
Primary failure of eruption (PFE) is a hereditary condition, and linkage with variants in the PTH1R gene has been demonstrated in many cases. The clinical severity and expression of PFE is variable, and the genotype-phenotype correlation remains elusive. Further, the similarity between some eruption disorders that are not associated with PTH1R alterations is striking. To better understand the genotype-phenotype correlation, we examined the relationship between the eruption phenotype and PTH1R genotype in 44 patients with suspected PFE and 27 unaffected relatives. Sanger sequencing was employed to analyze carefully selected PFE patients. Potential pathogenicity of variants was evaluated against multiple genetic databases for function prediction and frequency information.
Mutational analysis of the PTH1R coding sequence revealed 14 different variants in 38 individuals (30 patients and 8 first-degree relatives), 9 exonic and 5 intronic. Their pathogenicity has been reported and compared with the number and severity of clinical signs. In 72.7% of patients with pathogenic variants, five clinical and radiographic criteria have been found: involvement of posterior teeth, involvement of the distal teeth to the most mesial affected, supracrestal presentation, altered vertical growth of the alveolar process and posterior open-bite. In cases with mixed dentition (3), the deciduous molars of the affected quadrant were infraoccluded.
The probability of an affected patient having a PTH1R variant is greater when five specific clinical characteristics are present. The likelihood of an eruption defect in the absence of specific clinical characteristics is rarely associated with a PTH1R mutation.
We report here that systematic clinical and radiographic observation using a diagnostic rubric is highly valuable in confirming PFE and offers a reliable alternative for accurate diagnosis.
原发性萌出失败（PFE）是一种遗传性疾病，许多病例中已经证明与 PTH1R 基因的变体有关联。PFE 的临床严重程度和表现各不相同，基因型-表型相关性仍难以捉摸。此外，一些与 PTH1R 改变无关的萌出障碍之间的相似性令人瞩目。为了更好地理解基因型-表型相关性，我们检查了 44 名疑似 PFE 患者和 27 名无影响亲属的萌出表型与 PTH1R 基因型之间的关系。我们仔细选择 PFE 患者进行 Sanger 测序分析。使用多种遗传数据库评估变体的潜在致病性，以进行功能预测和频率信息。
对 PTH1R 编码序列的突变分析显示，在 38 个人（30 名患者和 8 名一级亲属）中发现了 14 种不同的变体，其中 9 种是外显子，5 种是内含子。它们的致病性已被报道，并与临床体征的数量和严重程度进行了比较。在 72.7%的致病性变异患者中，发现了五个临床和影像学标准：后牙受累、受累牙齿至最近侧受累的远中牙齿、牙冠上方呈现、牙槽骨垂直生长改变和后开颌。在混合牙列（3 例）中，受影响象限的乳牙下扣。
当存在五个特定的临床特征时，患有 PTH1R 变异的患者出现萌出缺陷的可能性更大。在缺乏特定临床特征的情况下，萌出缺陷发生的可能性很少与 PTH1R 突变相关。
我们在这里报告，使用诊断准则进行系统的临床和影像学观察对于确认 PFE 非常有价值，并提供了一种可靠的替代方法来进行准确诊断。
