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Targeted next-generation sequencing (NGS) analysis of mutations in nonsyndromic tooth agenesis candidate genes

Analysis of a Turkish cohort

Targeted NGS(„next-generation sequencing“)-Analyse von Mutationen in Kandidatengenen für nichtsyndromale Zahnaplasie

Analyse einer türkischen Kohorte

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

Abstract

Purpose

The goal of this study was to assess genes known to be associated with tooth agenesis with next-generation sequencing (NGS) and analyze the relationship between these mutations and tooth agenesis phenotypes.

Methods

The study included 49 individuals aged between 6 and 13 years. A total of 14 genes related to nonsyndromic tooth agenesis were selected for targeted NGS. Mutations in Msh homeobox 1 (MSX1), Wnt family member 10A (WNT10A), axis inhibition protein 2 (AXIN2), keratin 17 (KRT17), lipoprotein receptor 6 (LRP6), and secreted protein, acidic and rich in cysteine (SPARC)-related modular calcium-binding protein 2 (SMOC2) genes were investigated.

Results

Mutations in six genes were detected in 12 of 49 subjects. Fifteen variants were identified, including the unknown variants c.657G > C in MSX1, c.2029C > T in AXIN2, and c.1603A > T in LRP6. Second premolar tooth agenesis was observed in 43.3% of all tooth agenesis cases with mutations, and it was the predominant phenotype observed for each mutated gene, followed by tooth agenesis of the lateral incisors (20%).

Conclusions

Variations in MSX1, WNT10A, AXIN2, KRT17, LRP6, and SMOC2 may be a risk factor for hypodontia or oligodontia in the Turkish population.

Zusammenfassung

Zielsetzung

Ziel dieser Studie war es, als assoziiert mit Zahnagenesien bekannte Gene mittels NGS („next-generation sequencing“) zu untersuchen und den Zusammenhang zwischen diesen Mutationen und dem Phänotyp der Zahnagenesie zu analysieren.

Methoden

In die Studie wurden 49 Personen im Alter zwischen 6 und 13 Jahren eingeschlossen. Insgesamt wurden 14 mit nichtsyndromaler Zahnagenesie assoziierte Gene für ein gezieltes NGS ausgewählt. Untersucht wurden Mutationen in den Genen MSX1 („Msh homeobox 1“), WNT10A („Wnt family member 10A“), AXIN2 („axis inhibition protein 2“), KRT17 („keratin 17“), LRP6 („lipoprotein receptor 6“) und SMOC2 („SPARC[„secreted protein, acidic and rich in cysteine“]-related modular calcium-binding protein 2“).

Ergebnisse

Mutationen in 6 Genen wurden bei 12 von 49 Probanden nachgewiesen. Fünfzehn Varianten wurden identifiziert, darunter die unbekannten Varianten c.657G > C in MSX1, c.2029C > T in AXIN2, and c.1603A > T in LRP6. Eine Agenesie der zweiten Prämolaren wurde in 43,3 % aller Fälle mit Mutationen beobachtet und war der vorherrschende Phänotyp für jedes mutierte Gen, gefolgt von einer Agenesie der seitlichen Schneidezähne (20 %).

Schlussfolgerungen

Variationen in MSX1, WNT10A, AXIN2, KRT17, LRP6 und SMOC2 können ein Risikofaktor für Hypodontie oder Oligodontie in der türkischen Bevölkerung sein.

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Acknowledgements

Thanks for all the contributors and participants.

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Authors and Affiliations

  1. Department of Pediatric Dentistry, Gaziantep University, 27310, Gaziantep, Turkey

    Gül Keskin & Zübeyde Uçar Gündoğar

  2. Department of Medical Genetics, Pamukkale University, 20070, Denizli, Turkey

    Kadri Karaer

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  1. Gül Keskin
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Correspondence to Gül Keskin.

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G. Keskin, K. Karaer and Z. Uçar Gündoğar declare that they have no competing interests.

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The study protocol was approved by the Clinical Research Ethics Committee of Gaziantep University in Turkey. All participants and their parents were informed about the study, and consent forms were obtained.

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Keskin, G., Karaer, K. & Uçar Gündoğar, Z. Targeted next-generation sequencing (NGS) analysis of mutations in nonsyndromic tooth agenesis candidate genes. J Orofac Orthop 83 (Suppl 1), 65–74 (2022). https://doi.org/10.1007/s00056-021-00284-4

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