Die Rolle des Parathormonrezeptors Typ 1 bei der primären Zahndurchbruchsstörung

Zusammenfassung

Die primäre Zahndurchbruchsstörung (primary failure of tooth eruption, PFE) ist eine autosomal-dominante Erkrankung welche insbesondere zu einer Störung des Durchbruchs posteriorer Zähne führt und klinisch durch einen seitlich offenen Biss imponiert. Mittlerweile konnten eine Vielzahl von heterozygoten Mutationen des Typ 1 Parathormonrezeptors (PTH1R) mit dem Vorliegen einer PFE in Verbindung gebracht werden. Die Mutationen können alle funktionellen Bereiche des PTH1R erfassen, oder als Deletionsmutanten zu einem verkürzten Rezeptor führen. Erste Untersuchungen mittels in vitro Zellmodellen zeigten Änderungen der Lokalisation des mutierten Rezeptors und dominant negative Effekte auf den Wildtyp-PTH1R.

In diesem Übersichtsartikel werden die klinischen Charakteristika der PFE dargestellt und die Problematik der therapeutischen Optionen erörtert. Erste funktionelle Untersuchungen einzelner PTH1R-Mutanten werden erörtert.

Abstract

Primary failure of tooth eruption (PFE) is an autosomal dominant disease which mainly affects the eruption of posterior teeth leading to a lateral open bite. A variety of mutants of the type 1 parathormone receptor (PTH1R) was associated with clinical PFE. These mutations can be located in all functional regions of the PTH1R and may also lead to truncated receptors. First investigations with selected mutants using in vitro cell models showed changes of the cellular localization of the mutated receptors as well as dominant negative effects on the wild type PTH1R.

This short review summarizes the clinical characteristics of PFE and the problems of therapy. First functional investigations of PTH1R mutants will be discussed.

Schlüsselwörter

Primäre Zahndurchbruchsstörung - PTH1R - Mutationen

Key words

primary failure of tooth eruption (PFE) - PTH1R - Mutants

Publikationsverlauf

Eingereicht: 22. Januar 2022

Angenommen nach Revision: 08. April 2022

Artikel online veröffentlicht:
30. Mai 2022

• Literatur

• 1 Cahill DR, Marks SC. Tooth eruption: evidence for the central role of the dental follicle. J Oral Pathol 1980; 9: 189-200
• 2 Cahill DR, Marks SC, Wise GE, Gorski JP. A review and comparison of tooth eruption systems used in experimentation – a new proposal on tooth eruption. In: Davidovitch Z ed. The biological mechanisms of tooth eruption and root resorption. Birmingham, AL: EBSCO Media; 1988: 1-7
• 3 Marks SC, Cahill DR. Experimental study in the dog of the non-active role of tooth in the eruptive progress. Arch Oral Biol 1984; 29: 311-322
• 4 Wise GE, Frazier-Bowers S. D`Souza Cellular, molecular, and genetic determinants of tooth eruption. Crit Rev Oral Biol Med 2002; 13: 323-334
• 5 Proffit WR, Frazier-Bowers SA. Mechanisms and control of tooth eruption: overview and clinical implications. Orthod Craniofac Res 2009; 12: 59-66
• 6 Wise GE. Cellular and molecular basis of tooth eruption. Orthod Craniofac Res 2009; 12: 67-73
• 7 Raghoebar GM, Ten Kate LP, Hazenberg CA, Boering G, Vissink A. Secondary retention of permanent molars: a report of five families. J Dent 1992; 20: 277-282
• 8 O`Connell AC, Torske KT. Primary failure of tooth eruption. Oral Surg Oral Med Oral Pathol 1999; 87: 714-720
• 9 Proffit WR, Vig KW. Primary failure of eruption: a possible cause of posterior open-bite. Am J Orthod 1981; 80: 173-190
• 10 Pilz P, Meyer-Marcotty P, Eigenthaler M, Roth H, Weber BHF, Stellzig-Eisenhauer A. Differential diagnosis of primary failure of eruption (PFE) with and without evidence of pathogenic mutations in the PTHR1 gene. J Orofac Orthop 2014; 75: 226-239
• 11 Ahmad S, Bister D. et al. The clinical features and aetiological basis of primary eruption failure. Eur J Orthod 2006; 28: 535-540 Epub 2006 Oct 13
• 12 Decker E, Stellzig-Eisenhauer A, Fiebig BS. et al. PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am J Hum Genet 2008; 83: 781-786
• 13 Stellzig-Eisenhauer A, Decker E, Meyer-Marcotty P. et al. Primary failure of eruption (PFE)-clinical and molecular genetics analysis. J Orofac Orthop 2010; 71: 6-16
• 14 Roth H, Fritsche LG, Meier C. et al. Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption. Clin Oral Investig 2014; 18: 377-384
• 15 Jobert A-S, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C. Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest 1998; 102: 34-40
• 16 Duchatalet S, Ostergaard E, Cortes D, Lemainque A, Julier C. Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes. Hum Mol Genet 2005; 14: 1-5
• 17 Schipani E, Kruse K, Juppner H. A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science 1995; 286: 98-100
• 18 Hopyan S, Gokgoz N, Poon R. et al. A mutant PTH/PTHrP type I receptor in enchondromatosis. Nat Gen 2002; 30: 306-310
• 19 Rozeman LB, Sangiorgi L. et al. Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C. Hum Mutat 2004; 24: 466-473
• 20 Frazier-Bowers SA, Simmons D, Wright JT. et al. Primary failure of eruption and PTH1R: the importance of a genetic diagnosis for orthodontic treatment planning. Am J Orthod Dentofac Orthop 2010; 137: 160.e1-160.e7
• 21 Subramanian H, Döring F, Kollert S. et al. PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling. PLOS ONE 2016; 11: e0167033
• 22 Izumida E, Suzawa T. et al. Functional analysis of PTH1R variants found in primary failure of eruption. J Dent Res 2020; 99: 429-436
• 23 Hendricks HM, Bencharit S, Seaman W, Frazier-Bowers SA. In silico and functional evaluation of PTH1R mutations found in patients with primary failure of eruption (PFE). Orthod Craniofac Res 2017; 20 Suppl 1 57-62