Clinical phenotype and pathogenic gene study on a familial case with congenital premolar agenesis
10.13591/j.cnki.kqyx.2025.11.004
- VernacularTitle:1例先天前磨牙缺失家系的临床表型和致病基因研究
- Author:
Tingting CHENG
1
;
Xinyu ZHANG
;
Ji MAO
;
Shuangbo XU
;
Yongchu PAN
Author Information
1. 南京医科大学附属口腔医院正畸科,江苏南京(210029);口腔疾病研究与防治国家级重点实验室培育建设点,江苏南京(210029);江苏省口腔转化医学工程研究中心,江苏南京(210029)
- Publication Type:Journal Article
- Keywords:
congenital tooth agenesis;
whole-exome sequencing;
TTN
- From:
STOMATOLOGY
2025;45(11):819-825
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical phenotypic characteristics of a pedigree with congenital tooth agenesis(CTA)and identify the pathogenic gene using whole-exome sequencing(WES),aiming to confirm the disease-causing mutation site,explore its potential impact on protein structure and function,and provide new insights for the diagnosis of CTA.Methods The study focused on a pedigree with congenital absence of premolars.Blood samples were collected from pedigree members,and genomic DNA was extrac-ted.Potential pathogenic mutations were screened using WES and bioinformatics analysis.Candidate mutations were validated by Sanger sequencing.Gene Ontology(GO)functional annotation and KEGG pathway enrichment analysis were performed on co-expressed genes of the candidate gene.Results Clinical examination revealed that all four members of the family were patients with missing premolar teeth.WES identified two novel mutations in the TTN gene(c.94145G＞A and c.105406C＞T)in all affected family members.Sanger sequencing confirmed co-segregation of these mutations with the disease phenotype in the pedigree.Bioinformatics analysis indicated that Ttn was highly expressed during craniofacial development in mouse embryos.Enrichment analysis demonstrated that Ttn co-ex-pressed genes were significantly enriched in the extracellular matrix(ECM)receptor interaction and PI3K/Akt signaling pathway.Conclusion This study suggests that TTN is a potential pathogenic gene for congenital premolar agenesis in this pedigree.
