Detection Of Coding Region Mutations In PAX9, MSX1 And AXIN2 In Eleven Patients With Severe Oligodontia Phenotype

Background Congenital missing teeth is one of the most common human diseases. The incidence rate is 1.6%~20%. It can appear isolated in sporadic or familial ways, or can be associated with a syndrome. Oligodontia is a severe subtype of congenital missing teeth, with the performance of non-syndromes. The number of missing teeth are more than six, less than six are usually referred to tooth agenesis (hypodontia) ( excluding third molars). It is reported that the incidence of tooth abnormalities is about 0.08%~1.1%. The reasons of congenital missing teeth include two aspects: one is environmental factors, such as radiotherapy, multi-reagent chemotherapy, the other is genetic factor. It is considered that most cases of congenital missing teeth are related to genetic factor. In families, The inheritance patterns are autosomal dominant, autosomal recessive or X-linked recessive. The relationships among PAX9 (Paired box9), MSX1 (Msh homebox 1), AXIN2 (Axis inhibition protein2) and oligodontia are most clear. The correlated analysis of genotype-phenotype showed that clinical manifestations of MSXl gene mutation pedigree including non-syndromes and syndromes, as is often the combined with cleft lip and palate, involving the second premolars and third molars mainly; PAX9 gene mutation pedigree is about non-syndrome, commonly to lost molars. AXIN2 mutation is mainly sporadic case, as to the performance of MSX1 and PAX9. With the development of molecular biological experiments, the researches of human genetic diseases go greater depth. Teeth missing effect patients'chew, pronunciation function and facial appearance, with a dramatic impact on physical and mental health. The incidence of congenital missing teeth in Chinese people is high. But the relative progress in genetic research is poor. We use candidate gene approaches through collecting clinical cases, then target and screen mutations above three genes, furthermore elaborate the pathogenesis of congenital missing teeth. It is vital important to improve understandings of congenital missing teeth in Chinese people.Objective To detect the Pax9, Msx1 and Axin2 in eleven patients with severe oligodontia phenotype and explore the possible pathogenesis of congenital oligodontia.Methods We collected congenital missing teeth cases, designed questionnaires and investigated family history information. Systemic, oral specialist inspection and panoramic radiographs were collected to analyze clinical data, summarize its clinical characteristics, sorted family history, and analyzed genetic characteristics. After premising on informed consents, we extracted DNA from peripheral blood, then designed specificity primers about PAX9, MSX1 and AXIN2. Polymerization enzyme chain reaction (PCR) combining DNA direct bidirectional sequencing ways were adopted in former two genes, the latter gene was detected by PCR-single strand conformation polymorphism analytical (SSCP) technique.Results We collected 11 patients, aged 3 to 29 years old, including 4 males and 7 females. Missing teeth was from 8 to 27 (excluding third molars), Its average number was 17, involved in the second premolar and the second molar mainly, other teeth were to varying degrees. The same teeth loss in patients'upper and lower jaws were symmetry. We found an MSX1 single nucleotide polymorphic locus, but no PAX9, MSX1, AXIN2 mutations were discovered in 11 patients .Conclusions Considering the discrepancy between the high incidence rate of agenesis and the relatively small number of reported causative mutations in PAX9, MSX1 and AXIN2 genes, the genetic contribution to oligodontia probably is much more heterogeneous than expected so far.