Non-syndromic oligodontia

Abstract

Introduction. Oligodontia is defined as the developmental absence of more than six permanent teeth, not including third molars. The aetiology is genetic, a number of candidate genes for this condition have been identified, for instance Muscle segment homeobox 1 (MSXl), and Paired box 9 (P AX9). Mutations in these genes are associated mainly with the absence of premolar and molar teeth respectively. The reported prevalence of oligodontia is 0.08-0.16 %, however the clinical impression is that the prevalence in Malta may be higher. Materials and Methods. A survey of 1000 Dental Panoramic Tomograms from the archives of the Dental Department, Mater Dei Hospital, Malta revealed a prevalence of oligodontia of 0.8%. Two unrelated nuclear families and a further two unrelated individuals with oligodontia were tested at a genetic level. Saliva samples were collected and DNA extracted. Primers were designed to span the introns and intron-exon junctions of MSXl and P AX9, The primers were optimised using gradient PCR, and the samples genotyped by Real Time PCR followed by High Resolution Melting Analysis. DNA sequencing of all samples exhibiting a shift of the melting curve was carried out. Results. A misscnsc mutation (A40G) in lY1SXl (rs36059701), was found to segregate with the phenotype in both nuclear families. A novel missense mutation in P AX9 (A99P) was also found in two severely affected members of one family. Discussion and Conclusion. The MSXI A40G SNP is relatively common with a Minor Allele Frequency (MAF) of 0.20 in European populations, but has been associated with both Oligodontia and Cleft Palate. The PAX9 mutation is in the DNA binding domain (homeobox) and is predicted to be pathogenic. It is possible that the two genes act synergistically to produce the oligodontia phenotype.