20 Korean Peg-Lateralis Cohort

Peg-shaped lateral incisors are a common dental anomaly with a severe decrease in the mesiodistal diameter and tapering shape that occurs only in the maxillary arch. The genetics underlying this condition are poorly understood, particularly in cases without associated anomalies. We performed whole-exome sequencing (WES) to identify potential candidate genes contributing to the development of on-syndromic peg lateral incisors. Saliva samples were collected from 20 unrelated Korean individuals with non-syndromic peg lateral incisors that were not associated with other anomalies. WES was conducted on these samples, and variants were filtered using criteria of a p-value < 0.05, a false discovery rate < 10-10, and an odds ratio > 1. In silico mutation impact analysis was performed using Polymorphism Phenotyping v2, sorting intolerant from tolerant, and integrated score of co-evolution and conservation algorithms. We identified a heterozygous Oteopetrin-1(OTOP1) gene allele encoding the OTOP1 protein, a proton channel, in all 20 individuals. Gene Ontology analysis revealed an association between the OTOP1 gene and peg lateralis. We further confirmed that the peg lateralis candidate variant, rs199742451, of the same genotype was found in the family member of three subjects with the same phenotype. The results suggest a new possible function of OTOP1, which is yet to be studied, and identified it as a new candidate contributing to the development of peg lateralis. This study provides new insights into the genetic basis of non-syndromic peg lateralis and has important implications for further studies on the role of new genes in peg lateralis.