In this study, we sought to determine the association between tooth agenesis and DNA sequence variation in the genes MSX1 and PAX9 in an ethnically diverse human population. Since cleft lip/palate is also associated with both tooth agenesis and the gene TGFA, we included TGFA in the analysis as well. Cheek swab samples were obtained for DNA analysis from 116 case/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed by single-strand conformational polymorphism or kinetic polymerase chain-reaction assays. Transmission distortion of the marker alleles and DNA sequence analysis was performed. Results showed that tooth agenesis is associated with markers of the genes MSX1 and TGFA. No mutations were found in MSX1 or PAX9 coding regions. There were statistically significant data suggesting that MSX1 interacts with PAX9. These findings suggest that MSX1, PAX9, and TGFA play a role in isolated dental agenesis.

The NIH Consensus Development Program released a statement in 2001 (http://consensus.nih.gov/2001/2001DentalCaries115html.htm) and listed six major clinical caries research directions. One of these directions was the need for genetic studies to identify genes and genetic markers of diagnostic, prognostic and therapeutic value. This last decade has seen a steep increase in studies investigating the presence of genetic factors influencing individual susceptibility to caries. This review revisits recent caries human genetic studies and provides a perspective for future studies in order to fulfil their promise of revolutionizing our understanding of and the standard of care for the most prevalent bacteria-mediated non-contagious disease in the world.

The aim of this cross-sectional epidemiological survey was to assess the prevalence of dental trauma in athletes representing 42 countries competing at the most recent Pan American Games (XV Pan Am) held in Rio de Janeiro, Brazil in July of 2007, and to determine prior use and type of mouthguard among this group of athletes. The examiners participated in standardization and calibration training sessions before the field phase began. Invitations were sent to >5500 participating athletes competing in 41 sports and to the Medical Committee of the Pan American Sports Organization before and during the XV PAN. A convenience sample of 409 athletes was recruited. After signing an informed consent, all athletes answered a questionnaire. Data were collected at the clinical examination and recorded on a specific trauma form. The mean age of the athletes was 24.4 +/- 5.3 years. Males comprised 55% of the sample; females 45%. The prevalence of dental trauma among the athletes was 49.6% (n = 203) with no gender-based differences. Most of these injuries (63.6%) were related to activities during training or competition. Sports with the highest injury prevalence were wrestling (83.3%), boxing (73.7%), basketball (70.6%) and karate (60%). The most common injury was enamel fracture (39.8%); root fracture was the least common (0.4%). The teeth most affected were the maxillary permanent central incisors (n = 113), followed by the mandibular central incisors (n = 19). Based on the results of this study, nearly one-half of the subjects had experienced previous dental trauma; the majority related to sports activities. Furthermore, only 17% of the athletes reported prior mouthguard use; the most frequent mouthguards reported were boil-and-bite. These results suggest the importance of enhanced educational efforts and the use of properly fitted mouthguards to reduce dental trauma among athletes in international sports competition, especially in sports where mouthguards are not mandatory.

No abstract

Phenotypic characteristics expressed in syndromes give clues to the factors involved in the cause of isolated forms of the same defects. We investigated two genes responsible for craniofacial syndromes, FGFR1 and IRF6, in a collection of families with isolated tooth agenesis. Cheek swab samples were obtained for DNA analysis from 116 case/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. In addition, we studied 89 cases and 50 controls from Ohio to replicate any positive findings. Genotyping was performed by kinetic polymerase chain-reaction or TaqMan assays. Linkage disequilibrium analysis and transmission distortion of the marker alleles were performed. The same variants in the IRF6 gene that are associated with isolated orofacial clefts are also associated with human tooth agenesis (rs861019, P = 0.058; rs17015215-V274I, P = 0.0006; rs7802, P = 0.004). Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. The craniofacial phenotypic characteristics of these syndromes include oral clefts and preferential tooth agenesis of incisors and premolars, besides pits on the lower lips. Also it appears that preferential premolar agenesis is associated with FGFR1 (P = 0.014) and IRF6 (P = 0.002) markers. There were statistically significant data suggesting that IRF6 interacts not only with MSX1 (P = 0.001), but also with TGFA (P = 0.03).

MSX1 has been considered a strong candidate for orofacial clefting, based on mouse expression studies and knockout models, as well as association and linkage studies in humans. MSX1 mutations are also causal for hereditary tooth agenesis. We tested the hypothesis that individuals with orofacial clefting with or without tooth agenesis have MSX1 coding mutations by screening 33 individuals with cleft lip with or without cleft palate (CL/P) and 19 individuals with both orofacial clefting and tooth agenesis. Although no MSX1 coding mutations were identified, the known 101C>G variant occurred more often in subjects with both CL/P and tooth agenesis (p = 0.0008), while the *6C-T variant was found more often in CL/P subjects (p = 0.001). Coding mutations in MSX1 are not the cause of orofacial clefting with or without tooth agenesis in this study population. However, the significant association of MSX1 with both phenotypes implies that MSX1 regulatory elements may be mutated.

Tooth agenesis is a common congenital disorder that affects almost 20 percent of the world’s population. A number of different genes have been shown to be associated with cases of tooth agenesis including AXIN2, IRF6, FGFR1, MSX1, PAX9, and TGFA. Of particular interest is AXIN2, which was linked to two families segregating oligodontia and colorectal cancer. We studied two collections of families affected with tooth agenesis and tested them for association with AXIN2. Significant association between tooth agenesis and AXIN2 was found (p = 0.02) in cases with at least one missing incisor. Our work further supports a role of AXIN2 in human tooth agenesis and for the first time suggests AXIN2 is involved in sporadic forms of common incisor agenesis. Future studies should identify which specific tooth agenesis subphenotypes are consequence of AXIN2 genetic variations. A subset of these cases could have an increased susceptibility for colon cancer or other types of tumors and this knowledge would have significant clinical implications.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH’s development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.