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WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

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Abstract

Objectives

The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of cancer.

Materials and methods

We enrolled 60 young subjects (aged 13 to 17) from the Czech Republic with various forms of tooth agenesis. Dental phenotypes were assessed using Planmeca ProMax 3D (Planmeca Oy, Finland) with Planmeca Romexis software (version 2.9.2) together with oral examinations. After screening PAX9, MSX1, EDA, EDAR, AXIN2 and WNT10A genes on the Illumina MiSeq platform (Illumina, USA), we further analyzed the evolutionarily highly conserved WNT10A gene by capillary sequencing in the seven families.

Results

All the detected variants were heterozygous or compound heterozygous with various levels of phenotypic expression. The most severe phenotype (oligodontia) was found in a proband who was compound heterozygous for the previously identified WNT10A variant p.Phe228Ile and a newly discovered c.748G > A variant (p.Gly250Arg) of WNT10A. The newly identified variant causes substitution of hydrophobic glycine for hydrophilic arginine.

Conclusions

We suggest that the amino acid changes in otherwise highly conserved sequences significantly affect the dental phenotype. No relationship between the presence of WNT10A variants and a risk of cancer has been found.

Clinical relevance

Screening of PAX9, MSX1, EDA, EDAR, AXIN2 and WNT10A genes in hope to elucidate the pattern of inheritance in families.

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Acknowledgements

We would like to thank all the subjects who participated in the research. The authors thank Dr. Philip J. Coates (RECAMO, MMCI, Brno, Czech Republic) for English language editing.

Funding

This work was funded by grants of the IGA MH CZ n.: NT/11420–6/2010, the European Regional Development Fund-Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868), MH CZ-DRO (MMCI, 00209805) and AZV CR NU20-06–00189.

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Authors and Affiliations

  1. Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic

    Peter Bielik, Tomáš Zeman, Jan Lochman & Omar Šerý

  2. Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    Ondřej Bonczek & Bořivoj Vojtěšek

  3. Institute of Dentistry and Oral Sciences, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

    Přemysl Krejčí

  4. Laboratory of Neurobiology and Pathological Physiology, Institute of Animal Physiology and Genetics, The Academy of Sciences of the Czech Republic, Brno, Czech Republic

    Tomáš Zeman, Jan Lochman, Vladimir J. Balcar & Omar Šerý

  5. Department of Stomatology, Institution Shared With St. Anne’s University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech Republic

    Lydie Izakovičová-Hollá, Jana Šoukalová & Jiří Vaněk

  6. Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia

    Vladimir J. Balcar

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Contributions

All authors made substantial contribution to the conception and design of the manuscript. P.B. and O.B. drafted manuscript, T.Z. analyzed data from NGS sequencing, P.B. and J.L. performed NGS sequencing, P.K., J.S. and J.V. performed sampling and clinical investigations, J.V., L.I.H. and O.S. conceptualized research and obtained fundings, B.V. and V.J.B. edited and supervised manuscript, and O.S. supervised laboratory analyses and final manuscript. All authors agree to be accountable for all aspects of the study design and its content. All authors approved the final submitted version.

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Correspondence to Omar Šerý.

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The study protocol and informed consents were reviewed and approved by the ethical committee of Faculty of Medicine and Dentistry, Olomouc and Faculty of Medicine, Brno. The study was performed in accordance with the Declaration of Helsinki. Care was taken to follow the letter and spirit of the Declaration of Helsinki—ethical principles for medical research involving human subjects.

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Written informed consent (No: Fm-L009-001-ZUBNI-014) was obtained from all participating human subjects.

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Bielik, P., Bonczek, O., Krejčí, P. et al. WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer. Clin Oral Invest 26, 7045–7055 (2022). https://doi.org/10.1007/s00784-022-04664-x

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