Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome.

Kohlschütter-Tönz syndrome (KTS) is an autosomal-recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. The molecular basis has not yet been elucidated. Here, we report that KTS is caused by mutations in ROGDI. Using a combination of autozygosity mapping and exome sequencing, we identified a homozygous frameshift deletion, c.229_230del (p.Leu77Alafs(∗)64), in ROGDI in two affected individuals from a consanguineous family. Molecular studies in two additional KTS-affected individuals from two unrelated Austrian and Swiss families revealed homozygosity for nonsense mutation c.286C>T (p.Gln96(∗)) and compound heterozygosity for the splice-site mutations c.531+5G>C and c.532-2A>T in ROGDI, respectively. The latter mutation was also found to be heterozygous in the mother of the Swiss affected individual in whom KTS was reported for the first time in 1974. ROGDI is highly expressed throughout the brain and other organs, but its function is largely unknown. Possible interactions with DISC1, a protein involved in diverse cytoskeletal functions, have been suggested. Our finding that ROGDI mutations cause KTS indicates that the protein product of this gene plays an important role in neuronal development as well as amelogenesis.

Fluoride supplements (tablets, drops, lozenges or chewing gums) for preventing dental caries in children.

BACKGROUND: Dietary fluoride supplements were first introduced to provide systemic fluoride in areas where water fluoridation is not available. Since 1990, the use of fluoride supplements in caries prevention has been re-evaluated in several countries. OBJECTIVES: To evaluate the efficacy of fluoride supplements for preventing dental caries in children. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 12 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE via OVID (1950 to 12 October 2011), EMBASE via OVID (1980 to 12 October 2011), WHOLIS/PAHO/MEDCARIB/LILACS/BBO via BIREME (1982 to 12 October 2011), and Current Controlled Trials (to 12 October 2011). We handsearched reference lists of articles and contacted selected authors. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials comparing, with minimum follow-up of 2 years, fluoride supplements (tablets, drops, lozenges) with no fluoride supplement or with other preventive measures such as topical fluorides in children less than 16 years of age at the start. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (DMFS). DATA COLLECTION AND ANALYSIS: Two review authors, independently and in duplicate, assessed the eligibility of studies for inclusion, and carried out risk of bias assessment and data extraction. In the event of disagreement, we sought consensus and consulted a third review author. We contacted trial authors for missing information. We used the prevented fraction (PF) as a metric for evaluating the efficacy of the intervention. The PF is defined as the mean caries increment in controls minus mean caries increment in the treated group divided by mean caries increment in controls. We conducted random-effects meta-analyses when data could be pooled. We assessed heterogeneity in the results of the studies by examining forest plots and by using formal tests for homogeneity. We recorded adverse effects (fluorosis) when the studies provided relevant data. MAIN RESULTS: We included 11 studies in the review involving 7196 children.In permanent teeth, when fluoride supplements were compared with no fluoride supplement (three studies), the use of fluoride supplements was associated with a 24% (95% confidence interval (CI) 16 to 33%) reduction in decayed, missing and filled surfaces (D(M)FS). The effect of fluoride supplements was unclear on deciduous or primary teeth. In one study, no caries-inhibiting effect was observed on deciduous teeth while in another study, the use of fluoride supplements was associated with a substantial reduction in caries increment.When fluoride supplements were compared with topical fluorides or with other preventive measures, there was no differential effect on permanent or deciduous teeth.The review found limited information on the adverse effects associated with the use of fluoride supplements. AUTHORS' CONCLUSIONS: This review suggests that the use of fluoride supplements is associated with a reduction in caries increment when compared with no fluoride supplement in permanent teeth. The effect of fluoride supplements was unclear on deciduous teeth. When compared with the administration of topical fluorides, no differential effect was observed. We rated 10 trials as being at unclear risk of bias and one at high risk of bias, and therefore the trials provide weak evidence about the efficacy of fluoride supplements.

Rare dental peculiarities associated with the hypomyelinating leukoencephalopathy 4H syndrome/ADDH.

PURPOSE: 4H syndrome/ADDH, a disease of the cerebral white matter, seems to be associated with delayed tooth eruption and other dental abnormalities, which so far could not be assessed conclusively-mainly because patients were too young. The aim of this study was to characterize these abnormalities in a sample of patients old enough for a reliable assessment. METHODS: Three children, all diagnosed with 4H syndrome/ADDH, were followed from approximately 4 to 10 years of age and examined clinically and radiographically. In one case, a histopathological analysis supplemented these records. RESULTS: All 3 patients showed a generalized delay in eruption of the primary and permanent teeth, which culminated in complete retention of all primary maxillary central incisors. Permanent mandibular second premolars were missing in all children and permanent maxillary central incisors of 2 individuals exhibited a concave labial surface, while agenesis of the permanent maxillary lateral incisors and natal or neonatal teeth were observed in one patient. CONCLUSION: 4H syndrome/ADDH seems to be associated with a delay in primary tooth eruption, complete retention of the primary maxillary central incisors, and shape abnormalities of the permanent maxillary central incisors, which otherwise are very rare. Therefore, a neurological examination would appear warranted when these peculiarities are encountered.

An in vitro investigation to optimize the quality of compomer-based fissure sealants.

PURPOSE: To evaluate if the in vitro quality of preventive fissure sealants made with compomer-based materials can be improved by modifying the method of application. METHODS: Delton resin-based sealant, Dyract Flow and Dyract Seal compomers were used. The manufacturer's instructions were modified by prolonging the application time of the materials used and by applying the sealer in two layers. Extracted caries-free human molars were fissure sealed under standardized conditions and then exposed to a thermocycling procedure and a dye penetration test. Following the preparation of ground slices the samples were assessed by means of a light microscope and a scanning electron microscope. Statistical analysis of the results was done using a chi-square test. RESULTS: The modified application of the two-compomer-based fissure sealers improved distinctly the quality of such fissure sealants. This was observed with respect to the criteria sealing ability, absence of pores in the sealant and complete filling of the fissure in wide as well as in narrow fissures. Compomer-based fissure sealants applied with the modified technique were equal to conventional resin-based composite fissure sealants regarding sealing ability and complete filling of the fissure. With respect to absence of pores, compomer-based sealants were superior to resin-based composite sealants.

Effect of cavity preparation instruments (oscillating or rotating) on the composite-dentin interface in primary teeth.

OBJECTIVES: To evaluate the effect of preparation of instruments on the interfacial integrity between cavity wall and composite restoration. METHODS: Two class II slot preparations were done in 10 primary teeth either with SonicSys or with a conventional bur. The cavities were filled using an adhesive system. One layer of a flowable composite and one layer of a condensable composite were applied. The specimens were analyzed by confocal laser scanning microscopy. RESULTS: In the SonicSys group the mean thickness of the hybrid layer was 6.12 (0.60) microm; in the control group it was 6.04 (0.63) microm. The difference was not statistically significant. Two fractures were observed in one tooth of each group. These were located only in the enamel. The cavity margins were beveled in all specimens. SIGNIFICANCE: Compared to conventional preparations, cavity preparation with SonicSys has no deleterious effect on the integrity of the interface.

Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization.

Dentine dysplasia type II is an autosomal dominant disorder in which mineralization of the dentine of the primary teeth is abnormal. On the basis of the phenotypic overlap between, and shared chromosomal location with, dentinogenesis imperfecta type II, a second disorder of dentine mineralization, it has been proposed that the two conditions are allelic. As recent studies have shown that dentinogenesis imperfecta type II results from mutation of the bicistronic dentine sialophosphoprotein gene (DSPP ), we have tested this hypothesis by sequencing DSPP in a family with a history of dentine dysplasia type II. Our results have shown that a missense change, which causes the substitution of a tyrosine for an aspartic acid in the hydrophobic signal peptide domain of the protein, underlies the phenotype in this family. Biochemical analysis has further demonstrated that this mutation causes a failure of translocation of the encoded proteins into the endoplasmic reticulum, and is therefore likely to lead to a loss of function of both dentine sialoprotein and dentine phosphoprotein.