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Tooth ultrastructure changes induced by a nonsense mutation in the FAM83H gene: insights into the diversity of amelogenesis imperfecta

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Abstract

Objectives

The current research on single-nucleotide polymorphism (SNP) mutation sites at different positions of the FAM83H gene and their phenotypic changes leading to amelogenesis imperfecta (AI) is inconsistent. We identified a previously reported heterozygous nonsense mutation c.1192C>T (p.Q398*) in the FAM83H gene and conducted a comprehensive analysis of the dental ultrastructure and chemical composition changes induced by this mutation. Additionally, we predicted the protein feature affected by this mutation site. The aim was to further deepen our understanding of the diversity of AI caused by different mutation sites in the FAM83H gene.

Methods

Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient’s teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods.

Results

One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient’s dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients’ teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients’ teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site.

Conclusions

This study expands the understanding of the effects of FAM83H mutations on tooth structure.

Clinical relevance

Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Funding

This study was supported by the National Natural Science Foundation of China (81800788 and 81773339), Science and Technology Department of Hunan Province, China (2017WK2041, 2018SK52511, and 2022ZK4084), Scientific Research Project of Hunan Provincial Health Commission (202208043514 and B202308056340), Hunan Provincial Natural Science Foundation of China (2022JJ30062), Natural Science Foundation of Changsha City (kq2202403 and kq2202412), Fund for the Xiangya Clinical Medicine Database of Central South University (2014-ZDYZ-1-16), Education and Teaching Reform Research Project of Central South University (2020jy165-3), Research Project on Postgraduate Education and Teaching Reform of Central South University (2021JGB072), Hunan Provincial Innovation Foundation For Postgraduate (CX20220370), and The Fundamental Research Funds for the Central Universities of Central South University (2022ZZTS0913 and 2022ZZTS0912).

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Author notes

  1. Li Tan and Yue Guo contributed equally to this study.

Authors and Affiliations

  1. Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China

    Li Tan, Yue Guo, Meng-Mei Zhong, Ya-Qiong Zhao, Jie Zhao, Dusenge Marie Aimee, Yao Feng, Qin Ye, Jing Hu, Ze-Yue Ou-Yang, Ning-xin Chen, Xiao-Lin Su, Qian Zhang, Qiong Liu, Hui Yuan, Min-Yuan Wang, Yun-Zhi Feng & Feng-Yi Zhang

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  1. Li Tan
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Contributions

L.T. and Y.G. were in charge of task management and research conception. Q.L., M.-M.Z., M.-Y.W., N.-X.C., X.-N.S., Q.Z., H.Y., and Y.-Q.Z. were in charge of choosing the research topics and gathering the data. Y.-H.Z., Y.F., Q.Y., J.H., Z.-Y.O.-Y., D.-M.A., Y.-Z.F., and J.Z. conducted the statistical analyses. F.-Y.Z. supervised the project. Each author contributed to the analysis and writing of the publication.

Corresponding author

Correspondence to Feng-Yi Zhang.

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Ethical approval and consent

The Second Xiangya Hospital, Central South University’s Institutional Review Board granted approval for this study (No. 2021031), and the Declaration of Helsinki’s procedures were followed throughout (2008). Before collecting the sample, the patient’s informed consent was obtained.

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Tan, L., Guo, Y., Zhong, MM. et al. Tooth ultrastructure changes induced by a nonsense mutation in the FAM83H gene: insights into the diversity of amelogenesis imperfecta. Clin Oral Invest 27, 6111–6123 (2023). https://doi.org/10.1007/s00784-023-05228-3

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