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Identification of a novel missense heterozygous mutation in the KDF1 gene for non-syndromic congenital anodontia

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Abstract

Objectives

KDF1 is a recently identified gene related to tooth development, but it has been little studied. To date, only three cases have been reported in which KDF1 mutations are related to tooth development, including two ectodermal dysplasia cases accompanied by tooth loss and one non-syndromic case with tooth agenesis. However, no KDF1 mutations have been reported as associated with non-syndromic anodontia. Here, the aim was to investigate the genetic etiology of this condition and explore the functional role of a novel KDF1 mutation in a Chinese patient with non-syndromic anodontia.

Materials and methods

Pathogenic variants were identified by whole-exome and Sanger sequencing. Meanwhile, we conducted a literature review of the reported KDF1 mutations and performed an in vitro functional analysis of four anodontia-causing KDF1 mutations (one novel and three known).

Results

We identified a novel de novo missense mutation (c.911 T > A, p.I304N) in the KDF1 gene in a Chinese patient with severe non-syndromic anodontia. In vitro functional studies showed altered mRNA and protein expression levels of the mutant KDF1.

Conclusions

Our results are the first report of KDF1 missense mutation causing non-syndromic anodontia.

Clinical relevance

This study not only further supports the important role of KDF1 in non-syndromic congenital anodontia, but also expands the spectrum of KDF1 mutations and will contribute to the genetic diagnosis and counselling of families with anodontia.

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Funding

National Natural Science Foundation of China (31970558, 82170920), National Key S&T Special Projects (2021YFC1005301), Natural Science Foundation of Guangdong Province of China (2018B030311033), Health Department of Guangxi Zhuang Autonomous Region (Z20200678), Shenzhen Fundamental Research Program (JCYJ20180228164057158).

Author information

Author notes

  1. Yuhua Pan and Sheng Yi contributed equally to this work.

Authors and Affiliations

  1. School of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Yuhua Pan & Xinchen Yao

  2. Genetic and Metabolic Central Laboratory, Birth Defects Prevention and Control Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, China

    Sheng Yi

  3. Department of Stomatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Dong Chen

  4. Department of Stomatology, The People’s Hospital of Longhua, 38 Jinglong Jianshe Road, Longhua, Shenzhen, Guangdong, 518109, People’s Republic of China

    Xinya Du

  5. Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, 1838 Guangzhou North Avenue, Guangzhou, 510515, China

    Fei He & Fu Xiong

  6. Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, Guangdong, China

    Fu Xiong

  7. Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Fu Xiong

Authors
  1. Yuhua Pan
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  2. Sheng Yi
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Contributions

Yuhua Pan: conceptualization; methodology; formal analysis; writing—original draft; writing—review and editing. Sheng Yi: software, investigation, resources, funding acquisition. Dong Chen and Xinya Du: methodology, formal analysis, software. Xinchen Yao: resources, data curation. Fei He: visualization, supervision, project administration, funding acquisition. Fu Xiong: validation; writing—review and editing; project administration; funding acquisition.

Corresponding authors

Correspondence to Fei He or Fu Xiong.

Ethics declarations

Ethical approval

Approval was obtained from the Ethics Committee of Nanfang Hospital, an affiliate of Southern Medical University (No. NFEC-2021–1071). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Informed consent

Written informed consent was obtained from all participants or their guardians.

Conflict of interest

The authors declare no competing interests.

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Pan, Y., Yi, S., Chen, D. et al. Identification of a novel missense heterozygous mutation in the KDF1 gene for non-syndromic congenital anodontia. Clin Oral Invest 26, 5171–5179 (2022). https://doi.org/10.1007/s00784-022-04485-y

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  • DOI: https://doi.org/10.1007/s00784-022-04485-y

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