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Amelogenesis imperfecta in a Chinese family resulting from a FAM83H variation and the effect of FAM83H on the secretion of enamel matrix proteins

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Abstract

Objectives

To investigate the variant of an amelogenesis imperfecta (AI) family and to explore the function of the FAM83H (family with sequence similarity 83 member H) in the enamel formation.

Materials and methods

We investigated a five-generation Chinese family diagnosed with AI; clinical data was collected, whole-exome sequencing (WES) was conducted to explore the pathogenic gene and variants and Sanger sequencing was used to verify the variants. The three-dimensional protein structures of wild-type and mutant FAM83H were predicted using alpha fold 2. To study the possible regulatory function of Fam83h on amelogenesis, immunolocalization was performed to observe the expression of Fam83h protein in Sprague–Dawley rat postnatal incisors. The mRNA and protein level of amelogenin, enamelin, kallikrein-related peptidase-4 and ameloblastin were also detected after the Fam83h was knocked down by small interfering RNA (siRNA) in HAT-7 cells.

Results

A known nonsense variant (c.973 C > T) in exon 5 of FAM83H gene was found in this family, causing a truncated protein (p.R325X). Immunolocalization of Fam83h in Sprague–Dawley rat postnatal incisors showed that Fam83h protein expression was detected in presecretory and secretory stages. When Fam83h expression was reduced by siRNA, the expression of amelogenin, enamelin, kallikrein-related peptidase-4 decreased. However, the expression of ameloblastin increased.

Conclusions

FAM83H gene variant (c.973 C > T) causes AI. FAM83H regulates the secretion of enamel matrix proteins and affects ameloblast differentiation.

Clinical relevance

This study provided that FAM83H variants could influence enamel formation and provided new insights into the pathogenesis of AI.

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Funding

We thank the patients and their family members for consenting to this research. This study was funded by grants from the National Natural Science Foundation of China (82170947) and the Applied Foundation in Science and Technology Office of Sichuan Province (2021YFG0230).

Author information

Author notes

  1. Yongting Xie and Mingmei Meng equally contributed to this article and should be regarded as co-first authors.

Authors and Affiliations

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China

    Yongting Xie, Mingmei Meng, Qizhao Ma, Xiaojun Huang, Yue Yu, Qiyuan Yang & Jing Zou

  2. The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Centre for Medical Genetics, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology, Chengdu, Sichuan, China

    Li Cao & Jiyun Yang

  3. Department of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China

    Qin Du

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Contributions

JZ and QD contributed to the study conception and design. Bioinformatics and statistical analyses were performed by LC and JY. Clinical data collection and analysis were performed by QM, XH, YY and QY. Material preparation, experiment, data collection and analyses performed by YX and MM. The first draft of the manuscript was written by YX and MM, and all authors commented on previous versions of the manuscript. All authors read and approved the final.

Corresponding authors

Correspondence to Jing Zou or Qin Du.

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Competing interests

The authors declare no competing interests.

Ethical approval

This study was approved by the Ethics Committee of the Sichuan Academy of Medical Sciences-Sichuan Provincial People’s Hospital (Chengdu, China) [2020 (371)]. The animal experimental protocol was approved by the Ethics Committee of West China College of Stomatology, Sichuan University, Chengdu, China (WCHSIRB-D-2021–077).

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Informed consent was obtained from the legal guardians of children involved in the study.

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The authors declare no competing interests.

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Xie, Y., Meng, M., Cao, L. et al. Amelogenesis imperfecta in a Chinese family resulting from a FAM83H variation and the effect of FAM83H on the secretion of enamel matrix proteins. Clin Oral Invest 27, 1289–1299 (2023). https://doi.org/10.1007/s00784-022-04763-9

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