An evolution in methods of identifying the causal mutations and candidate genes for Mendelian disorders has occurred recently. Though several studies have reported the causative mutations in non syndromic tooth agenesis, there are only two reports on autosomal recessive nonsyndromic tooth agenesis in consanguineous families. Since the consanguinity rate is high in tribal population of Saudi and Pakistan, this study identified consanguineous families in these populations to investigate the molecular basis of tooth agenesis. This study aimed to study the phenotype of familial tooth agenesis in Saudi and Pakistani families of consanguineous marriage, and to identify the causative mutations. A further aim was to investigate the influence of the agenesis gene on tooth size in one large Saudi family. Sixteen families with non-syndromic tooth agenesis, were clinically characterised for the pattern of inheritance, tooth agenesis severity and type of teeth affected. Genetic analysis including homozygosity mapping and exome sequencing was performed in eight families. Hand measurements of Saudi family tooth dimensions were made on dental study models. The most affected tooth type in studied families were the lower second premolar and upper lateral incisors. The homozygosity mapping approach failed to identify the regions of the diseased mutations in these families. The exome sequencing data revealed a heterozygous novel frameshift mutation in exon 2 of the MSX1 gene, c.750_751insACCGGCTGCC (p.A250fs) in one Saudi family and a homozygous novel mutation in exon 8 of the SMOC2 gene, c.681T>A (p.C227X), in the Pakistani family. It was found that there was a significant (p <.0.05) trend of reduction in the crown sizes both in the tooth agenesis group and their family members with no tooth agenesis compared to the control group. It is concluded that homozygosity mapping was not sensitive to identify the elusive tooth agenesis gene and whole exome sequencing technique is needed in future studies. The tooth measurement study indicates and confirms that crown size is closely related to tooth agensis.

Salivary proteins such as statherin (STN) are known to be involved in enamel de/remineralisation, the inhibition of crystal growth, and spontaneous precipitation of calcium phosphate salts. The active N-terminal of STN (STN21) is involved in binding with Ca2+ and in reducing HA demineralisation. In addition, salivary Histatin-1 (HTN) inhibits crystal growth of calcium phosphate salts but does not inhibit their spontaneous precipitation. These salivary peptides do not occur as individual molecules in saliva, they are part of a complex salivary system. The aims were to investigate the effect of salivary STN, HTN and their 21 N-terminal peptides (STN21, and HTN21) individually and when in combination on the demineralisation rates of HA and enamel using scanning microradiography. In addition, to understand their effect on HA and enamel demineralisation, peptide adsorption onto HA and enamel was measured spectrophotometrically. Also, peptide aggregation, surface charge and, conformation in solution were investigated. The adsorption and demineralisation reduction of non-human STN was also investigated. STN, HTN and STN21 individually showed similar adsorption and demineralisation reduction efficacy in HA but not in enamel. HTN21 showed the lowest demineralisation reduction of all peptides. STN21 when in combination with either HTN, or HTN21, showed the greatest demineralisation reduction of all peptides. The increase in peptides demineralisation reduction efficacy when in combination suggests co-operative efficacy, which is further increased with the removal of the C-terminal. All individual peptides were found to adopt an α-helical conformation at the N-terminal, which is important in peptide adsorption onto HA surfaces. When in combination conformational changes led to peptide interaction and caused an increase in their net negative charges. In conclusion, it was found that the degree to which demineralisation is reduced by peptides is correlated with the amount of peptide adsorbed.

>Magister Scientiae - MSc / Background: Plaster models form an integral part of the traditional orthodontic records. They are necessary for diagnosis and treatment planning, case presentations as well as for the evaluation of treatment progress. The accuracy of the measurements taken for space assessment is crucial prior to treatment planning. The introduction of digital models overcomes some problems experienced with plaster models. Digital models have shown to be an acceptable alternative for plaster models. Aim: The aim of the study was to determine the accuracy of traditional measurement techniques when compared to the CAD/ CAM measurements in the assessment of tooth widths and arch perimeter from plaster models. Method: The mesio-distal tooth widths and arch perimeter of thirty archived plaster models were measured using a digital caliper to the nearest 0.01 mm and divider to the nearest 0.1 mm. Corresponding digital models were produced by scanning them with a CAD/CAM (InEos X5) and space analysis completed by measurements using InEos Blue software. Measurements were repeated after 1 week from the initial measurement. The methods were compared using descriptive analysis (mean difference and standard deviation). Results: The operator reliability was high for digital models as well as the plaster models when the measurement tool was the digital caliper (analyzed using the Pearson correlation coefficient in the paired t-test). The mean values of tooth widths measurements of CAD/CAM, digital caliper and divider were 6.82 (±0.04), 6.94 (± 0.04) and 7.11 (± 0.04). There was a significant difference between the measurements made by the CAD/CAM and the divider. Additionally significant differences between the measurements by digital caliper and divider measurements (p < 0.05) were observed. No significant difference was found when comparing CAD/CAM to digital caliper. Positive correlation was displayed between CAD/CAM, digital caliper and the divider, but the measurements completed with the digital caliper had the highest correlation with the CAD/CAM. The difference was not significant between the aforementioned measurement tools (p > 0.05). Arch perimeter measurements showed no statistical significant difference between CAD/CAM, digital caliper and divider (p < 0.05). Conclusion: Archived plaster models stored as records can be converted to digital models as it will have the same accuracy of measurements. The value of doing a space analysis with the CAD/CAM system can be performed with similar reliability on the digital models as a caliper on plaster models.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2018-09-27T17:56:21Z No. of bitstreams: 1 larissadeoliveirareis.pdf: 7026883 bytes, checksum: ed47575eca8cad23157546a9c709e3c8 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-10-16T12:14:27Z (GMT) No. of bitstreams: 1 larissadeoliveirareis.pdf: 7026883 bytes, checksum: ed47575eca8cad23157546a9c709e3c8 (MD5) / Made available in DSpace on 2018-10-16T12:14:27Z (GMT). No. of bitstreams: 1 larissadeoliveirareis.pdf: 7026883 bytes, checksum: ed47575eca8cad23157546a9c709e3c8 (MD5) Previous issue date: 2018-08-03 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O bruxismo em crianças e sua relação com o desenvolvimento das disfunções temporomandibulares (DTM) ainda não foram claramente definidos. O objetivo desta revisão sistemática foi avaliar a possível associação entre bruxismo e DTM em crianças. Sete bases de dados foram pesquisadas e 497 artigos foram avaliados. A qualidade metodológica foi avaliada através da Escala de Newcastle-Ottawa. A meta-análise foi realizada com os artigos em que a extração de dados foi possível e o efeito sumário foi medido por meio do odds ratio (OR) e respectivos intervalos de confiança de 95% (IC). A classificação de recomendações, avaliação, desenvolvimento e avaliação (GRADE) foi usada para avaliar a certeza da evidência. Dez estudos transversais foram incluídos na revisão sistemática. Destes, 8 apresentaram associação estatisticamente significante entre bruxismo e DTM. No entanto, 7 apresentaram alto risco de viés. A meta-análise foi realizada com 3 artigos e obteve OR de 2,97 (IC 95% variando de 1,72 a 5,15), indicando que crianças com bruxismo têm 2,97 vezes mais chances de apresentar DTM, com nível de certeza muito baixo definido pelo GRADE. Embora os estudos mostrem alto risco de viés, a análise qualitativa de estudos individuais mostrou que as crianças com bruxismo têm maior chance de desenvolver DTM. / Bruxism in children and its relation to the development of temporomandibular disorders (TMD) has not been clearly determined yet. The objective of this systematic review was to evaluate the possible association between bruxism and TMD in children. Seven databases were searched and 497 articles were assessed. Methodological quality was assessed through Newcastle-Ottawa Scale. The meta analysis was performed with the articles in which extraction of data was possible and the summary effect measure through odds ratio (OR) and respective 95% confidence intervals (CI). Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Ten cross sectional studies were included in the systematic review. Of these, 8 showed a statistically significant association between bruxism and TMD. However, 7 presented a high risk of bias. The meta-analysis was performed with 3 articles and obtained an OR of 2.97 (95% CI ranging from 1.72 - 5.15), indicating that children with bruxism are 2.97 times more likely to present TMD, with very low level of certainty defined by GRADE. Although the studies showed high risk of bias, the qualitative analysis of individual studies showed that the children with bruxism have greater chance of developing TMD.