Clinical, radiograpghic and genetic evaluation of Malaysian non-syndromic hypodontia patients

Abstract

Non-syndromic hypodontia is the developmental absence of one to six teeth that appears as an independent congenital oral trait. Its prevalence, pattern and distribution vary by population. To date, the majority of genetic mutations responsible for tooth agenesis have been identified in PAX9 and MSX1, genes encoding transcription factors that play a crucial role during odontogenesis. The aim of this study is to determine non-syndromic hypodontia clinically, radiographically and also its association with PAX9 and MSX1 mutations. 33 hypodontia patients were volunteered in this study. The patients were required to undergo clinical and radiographic examinations. Unstimulated saliva samples were collected for genetic screening purposes through a series of DNA extraction, amplification via PCR, purification and sequencing processes. Excluding the third molar, the most common missing tooth in maxilla and/or mandible are lateral incisors (30.5%) followed by second premolars (23.7%) and first premolars (20.3%). More missing teeth were identified at the mandible (50.8%), right side (54.2%), anterior region (54.2%) and also unilaterally (51.5%). Genetic assessment of PAX9 and MSX1 shows no mutation in all exons. Instead, two single nucleotide polymorphisms rs12881240 (His239) and rs4904210 (Ala240Pro) were identified in exon 3 of PAX9 gene. The SNPs are missense substitution (C>T) and synonymous codon (G>C, silent substitution) which was found in both case and control groups. However, rs12881280 association with hypodontia phenotype was not established due to unclear evidence His239 contributes or have influences on the risk of non-syndromic hypodontia occurrence. In contrast, rs4904210 may contribute to non-syndromic hypodontia phenotype due to its significant difference between the case and the control general population. For both SNPs, mild hypodonita is identified as the most common form of tooth agenesis in all affected individual. Nevertheless, many studies believed that differences in genetic variants including the SNPs found in this study are probably due to diversity in ethnic and population that cause inconsistency in different phenotype pattern and distribution of non-syndromic hypodontia.