关键词: 先天牙齿缺失, 全外显子组测序, TTN

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 extracted. 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-expressed 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.

Key words: congenital tooth agenesis, whole-exome sequencing, TTN