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Nonsyndromic oligodontia

Does the Tooth Agenesis Code (TAC) enable prediction of the causative mutation?

Non-syndromale Oligodontien

Kann anhand des Tooth Agenesis Code (TAC) die ursächliche Mutation vorhergesagt werden?

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Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie Aims and scope Submit manuscript

Abstract

Objectives

The literature suggests an association between phenotype and causative mutation in nonsyndromic oligodontia. Thus, the present study was designed to verify this hypothesis in a consecutive cohort of patients.

Methods

All patients with nonsyndromic oligodontia who had been treated at the study center (Department of Orthodontics, University of Giessen, Germany) over the period 1986–2013 were contacted. Candidates were included only if at least one more family member had hypo- or oligodontia (i.e., without regard to the number of congenitally missing teeth). A total of 20 patients were included. After evaluating the dental status of each participant, the Tooth Agenesis Code (TAC) was applied. On this basis, a tentative diagnosis was made to predict which gene (MSX1, AXIN2, EDA, or PAX9) was likely to show mutation. Afterwards this hypothesis was confirmed or rejected by analyzing a saliva sample for mutation of the predicted gene. If confirmed, any available family members were also genetically analyzed.

Results

Based on their TAC scores and sums, gene mutations were predicted for MXS1 in 11, AXIN2 in 3, EDA in 6, and PAX9 in none of the patients. The evaluation of MSX1 yielded variants in 4 of 11 cases, all of which were classified as nonpathogenic since they were not considered as functional mutations. The evaluation of EDA yielded a pathogenic exon-7 mutation in 2 of 6 patients, both being brothers with different TAC scores; the same mutation, which represents a novel missense mutation, was also found in other members of the same family. The evaluation of AXIN2 yielded variants in 3 of 3 cases, all of which were classified as nonpathogenic.

Conclusions

Our findings obtained in consecutive patients with nonsyndromic oligodontia did not reveal any clinically relevant associations between oligodontia phenotype (based on TAC) and causative mutations for nonsyndromic oligodontia.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war es, den in der Literatur für non-syndromale Oligodontien beschriebenen Zusammenhang zwischen Phänotyp und ursächlicher Mutation an einem konsekutiven Oligodontie-Patientengut zu verifizieren.

Material und Methode

Alle Patienten der Poliklinik für Kieferorthopädie (Justus-Liebig-Universität Gießen; Behandlung 1986–2013) mit non-syndromaler Oligodontie wurden kontaktiert. Außerdem musste mindestens ein weiterer Fall von Hypo-/Oligodontie in der Familie vorliegen. Nach Erhebung des Zahnstatus wurden die Nichtanlagedaten mit Hilfe des Tooth Agenesis Codes (TAC) analysiert und anschließend eine Prognose hinsichtlich von Mutationen der Gene MSX1, EDA, PAX9 und AXIN2 gestellt. Mittels Speichelproben erfolgte anschließend eine Mutationssuche im prognostizierten Gen. Bei positivem Untersuchungsergebnis wurden außerdem alle verfügbaren Familienmitglieder genetisch untersucht.

Ergebnisse

Insgesamt 20 Patienten wurden in die Studie aufgenommen. Auf Grundlage des TAC-Codes bzw. der TAC-Summen ergaben sich folgende Mutationsvermutungen: Bei 11 Patienten bestand der Verdacht auf eine Mutation in MSX1, bei 3 auf eine Mutation in AXIN2 und bei 6 auf eine Mutation in EDA. Bei keinem Patienten bestand Verdacht auf eine Mutation in PAX9. MSX1: Die Untersuchung ergab in 4 Fällen Varianten, die allerdings allesamt nicht als pathologisch einzustufen sind, da sie keine funktionelle Mutation verursachen. EDA: Zwei Patienten derselben Familie zeigten eine pathologische Mutation in Exon 7 des Gens, welche anschließend auch bei Familienangehörigen gefunden wurde und eine neue Punktmutation darstellt. AXIN2: Keiner der Patienten mit der Verdachtsdiagnose zeigte eine Mutation des Gens.

Schlussfolgerung

Im Rahmen der vorliegenden Untersuchung war es auf Basis des TAC für non-syndromal bedingte Oligodontien nur für 10% des konsekutiven Oligodontiepatientengutes möglich, einen Zusammenhang zwischen dem Phänotyp der Oligodentie und der ursächlichen Mutation darzustellen.

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Acknowledgements

The authors wish to thank the German Orthodontic Society (DGKFO) for providing support for this research project from its Science Fund.

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Authors and Affiliations

  1. Department of Orthodontics, University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany

    Niko C. Bock, Gisela Ruiz-Heiland & Sabine Ruf

  2. Private Practice, Lübeck, Germany

    Sarah Lenz

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  1. Niko C. Bock
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  2. Sarah Lenz
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  3. Gisela Ruiz-Heiland
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  4. Sabine Ruf
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Correspondence to Niko C. Bock.

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Conflict of interest

N. C. Bock, S. Jabir, G. Ruiz-Heiland, and S. Ruf declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Bock, N.C., Lenz, S., Ruiz-Heiland, G. et al. Nonsyndromic oligodontia. J Orofac Orthop 78, 112–120 (2017). https://doi.org/10.1007/s00056-016-0056-y

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  • DOI: https://doi.org/10.1007/s00056-016-0056-y

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