Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta

We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.746C>T, p.(P249L)) in ACPT, the gene encoding Acid Phosphatase, Testicular, which segregate with hypoplastic Amelogenesis imperfecta (AI) in two unrelated families. ACPT is reported to play a role in odontoblast differentiation and mineralisation by supplying phosphate during dentine formation. Analysis by computerised tomography and scanning electron microscopy of a primary molar tooth from an individual homozygous for the c.746C>T variant, revealed an enamel layer that was hypoplastic but mineralised with prismatic architecture. These findings implicate variants in ACPT as a cause of early failure of amelogenesis during the secretory phase

Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries

Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1–5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.Fil: Shimizu, T.. Nihon University of Dentistry; JapónFil: Deeley, K.. University of Pittsburgh; Estados UnidosFil: Briseño Ruiz, J.. University of Pittsburgh; Estados UnidosFil: Faraco Junior, I. M.. University of Pittsburgh; Estados UnidosFil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Brancher, J. A.. Pontifical Catholic University of Paraná; BrasilFil: Pecharki, G. D.. Pontifical Catholic University of Paraná; BrasilFil: Küchler, E. C.. Universidade Federal Fluminense; BrasilFil: Tannure, P. N.. Universidade Federal do Rio de Janeiro; BrasilFil: Lips, A.. Universidade Federal do Rio de Janeiro; BrasilFil: Vieira, T. C. S.. Universidade Federal Fluminense; BrasilFil: Patir, A.. Istanbul Medipol Universit; TurquíaFil: Yildirim, M.. Istanbul University; TurquíaFil: Mereb, J. C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Resick, J. M.. University of Pittsburgh; Estados UnidosFil: Brandon, C. A.. University of Pittsburgh; Estados UnidosFil: Cooper, M. E.. University of Pittsburgh; Estados UnidosFil: Seymen, F.. Istanbul University; TurquíaFil: Costa, M. C.. Universidade Federal do Rio de Janeiro; BrasilFil: Granjeiro, J. M.. Universidade Federal Fluminense; BrasilFil: Trevilatto, P. C.. Pontifical Catholic University of Paraná; BrasilFil: Orioli, I. M.. Universidade Federal do Rio de Janeiro; Brasil. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Castilla, Eduardo Enrique. Instituto Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Marazita, M. L.. University of Pittsburgh; Estados UnidosFil: Vieira, A. R.. University of Pittsburgh; Estados Unido

Detection of Streptococcus mutans Genomic DNA in Human DNA Samples Extracted from Saliva and Blood

Caries is a multifactorial disease, and studies aiming to unravel the factors modulating its etiology must consider all known predisposing factors. One major factor is bacterial colonization, and Streptococcus mutans is the main microorganism associated with the initiation of the disease. In our studies, we have access to DNA samples extracted from human saliva and blood. In this report, we tested a real-time PCR assay developed to detect copies of genomic DNA from Streptococcus mutans in 1,424 DNA samples from humans. Our results suggest that we can determine the presence of genomic DNA copies of Streptococcus mutans in both DNA samples from caries-free and caries-affected individuals. However, we were not able to detect the presence of genomic DNA copies of Streptococcus mutans in any DNA samples extracted from peripheral blood, which suggests the assay may not be sensitive enough for this goal. Values of the threshold cycle of the real-time PCR reaction correlate with higher levels of caries experience in children, but this correlation could not be detected for adults

Detection of Streptococcus mutans Genomic DNA in Human DNA Samples Extracted from Saliva and Blood

Caries is a multifactorial disease, and studies aiming to unravel the factors modulating its etiology must consider all known predisposing factors. One major factor is bacterial colonization, and Streptococcus mutans is the main microorganism associated with the initiation of the disease. In our studies, we have access to DNA samples extracted from human saliva and blood. In this report, we tested a real-time PCR assay developed to detect copies of genomic DNA from Streptococcus mutans in 1,424 DNA samples from humans. Our results suggest that we can determine the presence of genomic DNA copies of Streptococcus mutans in both DNA samples from caries-free and caries-affected individuals. However, we were not able to detect the presence of genomic DNA copies of Streptococcus mutans in any DNA samples extracted from peripheral blood, which suggests the assay may not be sensitive enough for this goal. Values of the threshold cycle of the real-time PCR reaction correlate with higher levels of caries experience in children, but this correlation could not be detected for adults

An example of secondary fault activity along the North Anatolian Fault on the NE Marmara Sea Shelf, NW Turkey

Seismic data on the NE Marmara Sea Shelf indicate that a NNE-SSW-oriented buried basin and ridge system exist on the sub-marine extension of the Paleozoic Rocks delimited by the northern segment of the North Anatolian Fault (NS-NAF), while seismic and multi-beam bathymetric data imply that four NW-SE-oriented strike-slip faults also exist on the shelf area. Seismic data indicate that NW-SE-oriented strike-slip faults are the youngest structures that dissect the basin-ridge system. One of the NW-SE-oriented faults (F1) is aligned with a rupture of the North Anatolian Fault (NAF) cutting the northern slope of the Cinarcik Basin. This observation indicates that these faults have similar characteristics with the NS-NAF along the Marmara Sea. Therefore, they may have a secondary relation to the NAF since the principle deformation zone of the NAF follows the Marmara Trough in that region. The seismic energy recorded on these secondary faults is much less than that on the NAF in the Marmara Sea. These faults may, however, produce a large earthquake in the long term

Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta

Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the developing enamel matrix pH. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with Amelogenesis Imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion and a missense) were predicted to result in loss of function. GPR68 encodes a proton sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localisation of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation

Genetic mapping of high caries experience on human chromosome 13

Background: Our previous genome-wide linkage scan mapped five loci for caries experience. The purpose of this study was to fine map one of these loci, the locus 13q31.1, in order to identify genetic contributors to caries.Methods: Seventy-two pedigrees from the Philippines were studied. Caries experience was recorded and DNA was extracted from blood samples obtained from all subjects. Sixty-one single nucleotide polymorphisms (SNPs) in 13q31.1 were genotyped. Association between caries experience and alleles was tested. We also studied 1,481 DNA samples obtained from saliva of subjects from the USA, 918 children from Brazil, and 275 children from Turkey, in order to follow up the results found in the Filipino families. We used the AliBaba2.1 software to determine if the nucleotide changes of the associated SNPs changed the prediction of the presence of transcription-binding site sequences and we also analyzed the gene expression of the genes selected based on binding predictions. Mutation analysis was also performed in 33 Filipino individuals of a segment of 13q31.1 that is highly conserved in mammals.Results: Statistically significant association with high caries experience was found for 11 markers in 13q31.1 in the Filipino families. Haplotype analysis also confirmed these results. In the populations used for follow-up purposes, associations were found between high caries experience and a subset of these markers. Regarding the prediction of the transcription-binding site, the base change of the SNP rs17074565 was found to change the predicted-binding of genes that could be involved in the pathogenesis of caries. When the sequence has the allele C of rs17074565, the potential transcription factors binding the sequence are GR and GATA1. When the subject carries the G allele of rs17074565, the potential transcription factor predicted to bind to the sequence is GATA3. The expression of GR in whole saliva was higher in individuals with low caries experience when compared to individuals with high caries experience (p = 0.046). No mutations were found in the highly conserved sequence.Conclusions: Genetic factors contributing to caries experience may exist in 13q31.1. The rs17074565 is located in an intergenic region and is predicted to disrupt the binding sites of two different transcription factors that might be involved with caries experience. GR expression in saliva may be a biomarker for caries risk and should be further explored. © 2013 Küchler et al.; licensee BioMed Central Ltd