Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (3): 92-98.doi: 10.6040/j.issn.1671-7554.0.2024.1342

• Clinical Medicine • Previous Articles    

Genetic analysis and literature review of a case of non-syndromic tooth agenesis caused by compound heterozygous mutations in WNT10A

DING Tingting1, LIU Haochen2   

  1. 1. Department of Stomatology, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing 100045, China;
    2. Department of Prosthodontics, Peking University School and Hospital of Stomatology &
    National Center for Stomatology &
    National Clinical Research Center for Oral Diseases &
    National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &
    Central Laboratory, Beijing 100081, China
  • Published:2025-04-08

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Abstract: Objective To investigate the pathogenic gene mutations in a patient with non-syndromic tooth agenesis(NSTA)and analyze the characteristics of tooth absence. Methods Blood samples were collected from the patients family and normal controls, and DNA was extracted. Whole exon sequencing(WES)and Sanger sequencing were used to identify and verify the pathogenic gene mutations. Functional impacts of the mutations were analyzed using the prediction software Polyphen-2, Mutation Taster, CADD, and fathmm. Conservation analysis and protein three-dimensional structure analysis were used to predict the effects of the mutations on protein function. Previously published literature was reviewed to analyze the tooth agenesis phenotypes associated with the mutated gene. Results Rare compound heterozygous mutations in WNT10A(c.637G>A/p.Gly213Ser and c.1009G>T/p.Val337Phe)in a patient with NSTA were identified, with the c.1009G>T mutation being novel. Polyphen-2, CADD, and fathmm predicted both mutations to be deleterious; Mutation Taster predicted c.637G>A to be benign and c.1009G>T to be deleterious. Conservation analysis showed that both mutation sites(213Gly and 337Val)were highly conserved through evolution, and three-dimensional structure analysis of the proteins indicated that the amino acid changes(p.Gly213Ser and p.Val337Phe)affected protein function. 142 cases of NSTA caused by WNT10A mutations were reviewed, and it is found that tooth loss was bilaterally symmetrical. The most frequently missing tooth positions were the mandibular second premolar(60.2%), maxillary second premolar(58.5%), and maxillary lateral incisor(53.9%); the least frequently missing tooth positions were the maxillary central incisor(2.1%), mandibular first molar(12.0%), and maxillary first molar(12.3%). Conclusion This study identified compound heterozygous mutations in WNT10A(c.637G>A/p.Gly213Ser and c.1009G>T/p.Val337Phe)in a Chinese patient with NSTA, with the c.1009G>T(p.Val3337Phe)variant being reported for the first time, thus expanding the mutation spectrum of the WNT10A gene. In addition, phenotypic analysis of WNT10A-related NSTA provides valuable insights for clinical diagnosis, treatment, and genetic counseling.

Key words: Non-syndromic tooth agenesis, Gene mutation, WNT10A, Genotype-phenotype analysis, Genetic counseling

CLC Number: 

  • R574
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