Primary failure of eruption: combined vision between paediatric dentist and orthodontist

Abstract Background 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. Results 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. Discussion 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. Conclusions 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.

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Novel Mutations in PTH1R Associated with Primary Failure of Eruption and Osteoarthritis

Journal of Dental Research ◽

10.1177/0022034513513588 ◽

2013 ◽

Vol 93 (2) ◽

pp. 134-139 ◽

Cited By ~ 32

Author(s):

S.A. Frazier-Bowers ◽

H.M. Hendricks ◽

J.T. Wright ◽

J. Lee ◽

K. Long ◽

...

Keyword(s):

Novel Mutations ◽

Primary Failure Of Eruption

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Primary failure of eruption: Clinical and genetic findings in the mixed dentition

The Angle Orthodontist ◽

10.2319/062717-430.1 ◽

2018 ◽

Vol 88 (3) ◽

pp. 275-282 ◽

Cited By ~ 5

Author(s):

Cristina Grippaudo ◽

Concetta Cafiero ◽

Isabella D'Apolito ◽

Beatrice Ricci ◽

Sylvia A. Frazier-Bowers

Keyword(s):

Clinical Evidence ◽

Mutational Analysis ◽

Mixed Dentition ◽

Permanent Teeth ◽

Phenotype Correlation ◽

Posterior Teeth ◽

Coding Regions ◽

Primary Failure Of Eruption ◽

Parathyroid Hormone 1 Receptor ◽

In Silico Analyses

ABSTRACT Objective: To test the hypothesis that mutations in the parathyroid hormone 1 receptor (PTH1R) include effects in both primary and permanent teeth. Materials and Methods: DNA was extracted from saliva samples of 29 patients (8 familial and 21 sporadic) who presented with clinical evidence of infraoccluded teeth, and their unaffected relatives (N = 22). Sequencing followed by mutational analysis of the coding regions of PTH1R gene was completed for all individuals (N = 29). Results: Eight of 29 cases revealed a heterozygous pathogenic variant in the PTH1R gene; five of eight variants represented distinct mutations based on comparison with the dbSNP, HGMD, and ESP databases. One mutation (c.1765 T>C p.Trp89Arg) was found to segregate within a family (n = 3). In silico analyses for all variants revealed a putative pathogenic effect. A genotype-phenotype correlation was reported as defined by a functional mutation in PTH1R and corresponding effects on one or more posterior teeth only; unilateral or bilateral involvement, infraoccluded primary teeth. Conclusions: Novel mutations were reported in the PTH1R gene that included PFE-affected primary molars, thus providing the basis for using a genetic diagnostic tool for early diagnosis leading to proper management.

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Primary Failure of Eruption (PFE) and ankylosis of permanent molars: the surgeon’s experience

Journal of Dentofacial Anomalies and Orthodontics ◽

10.1051/odfen/2015022 ◽

2015 ◽

Vol 18 (4) ◽

pp. 407 ◽

Cited By ~ 1

Author(s):

D. Deffrennes ◽

J. Cohen-Lévy

Keyword(s):

Primary Failure Of Eruption ◽

Permanent Molars

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A novel nonsense PTH1R variant shows incomplete penetrance of primary failure of eruption: a case report

BMC Oral Health ◽

10.1186/s12903-019-0944-9 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Cristina Grippaudo ◽

Concetta Cafiero ◽

Isabella D’Apolito ◽

Agnese Re ◽

Maurizio Genuardi ◽

...

Keyword(s):

Stop Codon ◽

Clinical Manifestations ◽

Premature Stop Codon ◽

Diagnostic Value ◽

Open Bite ◽

Incomplete Penetrance ◽

Functional Protein ◽

Case Presentation ◽

Primary Failure Of Eruption ◽

Buccal Swabs

Abstract Background Aim of this work was to describe a rare inheritance pattern of Primary Failure of Eruption (PFE) in a small family with incomplete penetrance of PFE and a novel nonsense PTH1R variant. Case presentation The proband, a 26 year-old man with a significant bilateral open-bite, was diagnosed with PFE using clinical and radiographic characteristics. DNA was extracted from the proband and his immediate family using buccal swabs and the entire PTH1R coding sequence was analyzed, revealing a novel heterozygous nonsense variant in exon 7 of PTH1R (c.505G > T). This variant introduces a premature stop codon in position 169, predicted to result in the production of a truncated and non-functional protein. This variant has never been reported in association with PFE and is not present in the Genome Aggregation Database (gnomAD). Interestingly, the c.505G > T variant has also been identified in the unaffected mother of our proband, suggesting incomplete penetrance of PFE. Conclusions In this study, we report a new PTH1R variant that segregates in an autosomal dominant pattern and causes PFE with incomplete penetrance. This underlines the diagnostic value of a thorough clinical and genetic analysis of all family members in order to estimate accurate recurrence risks, identify subtle clinical manifestations and provide proper management of PFE patients.

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