Differential diagnosis of primary failure of eruption (PFE) with and without evidence of pathogenic mutations in the PTHR1 gene
Differential diagnosis of primary failure of eruption (PFE) with and without evidence of pathogenic mutations in the PTHR1 gene
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DOI：
10.1007/s00056-014-0215-y
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发表时间：
2014-05-01
影响因子：
1.7
通讯作者：
Stellzig-Eisenhauer, Angelika
中科院分区：
文献类型：
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作者：
Pilz, Peter;Meyer-Marcotty, Philipp;Stellzig-Eisenhauer, Angelika
原发性出疹失败(PFE)可能与PTHR1基因突变有关。它有多种表现，以严重的后牙开放性咬合为特征。然而，也有与已知致病PTHR1突变无关的表型相似类型的出疹异常。本研究的目的是评估是否可以根据临床和放射学发现区分PTHR1突变携带者和非携带者。纳入36例疑似PFE患者，并根据特定的临床和放射学标准进行分析。此外，所有患者都进行了PTHR1基因所有编码序列(以及紧邻的内含子序列)的Sanger DNA测序分析，其中23例患者PTHR1基因存在杂合性致病突变(PTHR1突变携带者)，而另外13例患者(非PTHR1突变携带者)分子遗传学分析显示PTHR1基因无序列改变。携带者组中有5例患者有相关家族史，因此，本组共包括13例家族性病例和10例单纯性病例。这组非携带者没有透露相关的家族史。携带者组的所有患者都符合本研究中探讨的六个临床和放射标准：(1)后牙更常受到影响；(2)前牙萌出障碍并伴有额外的后牙受累；(3)受累牙齿吸收位于其冠状位置的牙槽骨；(4)乳牙和恒牙均受累；(5)垂直牙槽突生长受损；(6)严重的后牙张开咬合。相比之下，非携带者组的所有患者都不符合所分析的标准。携带者组中的所有患者都可以被归类为三种类型中的一种，表明皮疹发作的程度，而13名非携带者中有4人没有这三种类型。在本研究中采用的临床和放射学标准可以正确地确定非携带者组中13例PFE患者中有10例没有检测到PTHR1突变。临床和放射学特征的评估可以提高排除PFE患者可疑PTHR1参与的特异性。PTHR1相关的PFE的遗传因素是明显可识别的。需要更多的患者进行更多的研究，以优化这一初步方法在多变量分析中区分PTHR1突变携带者和非携带者的敏感性。
Primary failure of eruption (PFE) may be associated with pathogenic mutations in the PTHR1 gene. It has numerous manifestations and is characterized by severe posterior open bite. However, there are also phenotypically similar types of eruption anomalies not associated with a known pathogenic PTHR1 mutation. The purpose of this study was to evaluate whether a distinction can be made between PTHR1-mutation carriers and noncarriers based on clinical and radiological findings.A total of 36 patients with suspected PFE diagnoses were included and analyzed in accordance with specific clinical and radiographic criteria. In addition, all patients underwent Sanger DNA sequencing analysis of all coding sequences (and the immediate flanking intronic sequences) of the PTHR1 gene.Of these patients, 23 exhibited a heterozygous pathogenic mutation in the PTHR1 gene (PTHR1-mutation carriers), while molecular genetic analysis revealed nosequence alteration in the other 13 patients (non-PTHR1-mutation carriers). Relevant family histories were obtained from 5 patients in the carrier group; hence, this group included a total of 13 familial and 10 simplex cases. The group of noncarriers revealed no relevant family histories. All patients in the carrier group met six of the clinical and radiographic criteria explored in this study: (1) posterior teeth more often affected; (2) eruption disturbance of an anterior tooth in association with additional posterior-teeth involvement; (3) affected teeth resorbing the alveolar bone located coronal to them; (4) involvement of both deciduous and permanent teeth; (5) impaired vertical alveolar-process growth; and (6) severe subsequent finding of posterior open bite. None of the analyzed criteria were, by contrast, met by all patients in the noncarrier group. All patients in the carrier group could be assigned to one of three classifications indicating the extent of eruption disturbance, whereas 4 of the 13 noncarriers presented none of these three patterns. The clinical and radiographic criteria employed in this study would have correctly identified 10 of the 13 PFE patients in the noncarrier group as possessing no detectable PTHR1 mutation.The evaluation of clinical and radiographic characteristics can heighten the specificity of ruling out suspected PTHR1 involvement in PFE patients. A hereditary element of PTHR1-associated PFE is clearly identifiable. More studies with more patients are needed to optimize the sensitivity of this preliminary approach on the differential identification of PTHR1-mutation carriers versus noncarriers by multivariate analysis.