Search

Prosthodontic treatment of developmental age patients presents a significant challenge to the dentist. The growth and development of the stomatognathic system must be considered in treatment planning. Temporary prosthetic restorations must be regularly inspected and recemented, and final prosthetic restoration should not be delivered until the growth of the body is complete. In addition, due to the complex nature of morphological and functional disorders during the developmental period, simultaneous prosthetic and orthodontic treatment may be required. The case presented in this article is a 16-year-old boy with severe tooth destruction caused by untreated caries disease and poor oral hygiene. The patient required conservative, endodontic, and surgical treatment to restore the occlusion and aesthetics to allow the proper development of the masticatory organ. This article also presents the treatment case of a young patient with damaged crowns in the upper arch, which were restored with standard root-crown posts and cores and temporary 3D-printed composite crowns.

Non-syndromic cleft palate (ns-CP) has a genetically heterogeneous aetiology. Numerous studies have suggested a crucial role of rare coding variants in characterizing the unrevealed component of genetic variation in ns-CP called the "missing heritability". Therefore, this study aimed to detect low-frequency variants that are implicated in ns-CP aetiology in the Polish population. For this purpose, coding regions of 423 genes associated with orofacial cleft anomalies and/or involved with facial development were screened in 38 ns-CP patients using the next-generation sequencing technology. After multistage selection and prioritisation, eight novel and four known rare variants that may influence an individual's risk of ns-CP were identified. Among detected alternations, seven were located in novel candidate genes for ns-CP, including COL17A1 ( c.2435-1G>A), DLG1 (c.1586G>C, p.Glu562Asp), NHS ( c.568G>C, p.Val190Leu-de novo variant), NOTCH2 (c.1997A>G, p.Tyr666Cys), TBX18 (c.647A>T, p.His225Leu), VAX1 (c.400G>A, p.Ala134Thr) and WNT5B (c.716G>T, p.Arg239Leu). The remaining risk variants were identified within genes previously linked to ns-CP, confirming their contribution to this anomaly. This list included ARHGAP29 (c.1706G>A, p.Arg569Gln), FLNB (c.3605A>G, Tyr1202Cys), IRF6 (224A>G, p.Asp75Gly-de novo variant), LRP6 (c.481C>A, p.Pro161Thr) and TP63 (c.353A>T, p.Asn118Ile). In summary, this study provides further insights into the genetic components contributing to ns-CP aetiology and identifies novel susceptibility genes for this craniofacial anomaly.

(1) Background: Modern imaging methods and constantly developing technologies extend the range of diagnostic tools in medicine and in orthodontics. Thanks to them, scientists and doctors can use devices designed to diagnose 3D structures of the human body. The aim of the study was to assess the usefulness of digital orthodontic models as a diagnostic tool in the work of an orthodontist through a comparative analysis of the value of orthodontic measurements made on traditional plaster models and virtual models. (2) Methods: A total of 80 sets of models were made, including 40 sets of plaster models and 40 sets of digital models. A total of 48 diagnostic parameters were developed. They concerned dental parameters. (3) Results: Comparative analysis of crown height values on plaster and digital models showed statistically significant differences ( p < 0.05) in 26 out of 48 dental parameters. (4) Conclusions: The differences between the measurements made with the software on the digital models and the measurements made with the traditional method of measurement using the digital caliper on the plaster models were small and clinically acceptable., Competing Interests: The authors declare no conflict of interest.

Many unbalanced large copy number variants reviewed in the paper are associated with syndromic orofacial clefts, including a 1.6 Mb deletion on chromosome 3q29. The current report presents a new family with this recurrent deletion identified via whole-exome sequencing and confirmed by array comparative genomic hybridization. The proband exhibited a more severe clinical phenotype than his affected mother, comprising right-sided cleft lip/alveolus and cleft palate, advanced dental caries, heart defect, hypospadias, psychomotor, and speech delay, and an intellectual disability. Data analysis from the 3q29 registry revealed that the 3q29 deletion increases the risk of clefting by nearly 30-fold. No additional rare and pathogenic nucleotide variants were identified that could explain the clefting phenotype and observed intrafamilial phenotypic heterogeneity. These data suggest that the 3q29 deletion may be the primary risk factor for clefting, with additional genomic variants located outside the coding sequences, methylation changes, or environmental exposure serving as modifiers of this risk. Additional studies, including whole-genome sequencing or methylation analyses, should be performed to identify genetic factors underlying the phenotypic variation associated with the recurrent 3q29 deletion., (© 2022 Wiley Periodicals LLC.)

Panoramic radiograph is a universally used diagnostic method in dentistry for identifying various dental anomalies and assessing developmental stages of the dentition. The second premolar is the tooth with the highest number of developmental abnormalities. The purpose of this study was to generate neural models for assessing the position of the bud of the second premolar tooth based on analysis of tooth-bone indicators of other teeth. The study material consisted of 300 digital pantomographic radiographs of children in their developmental period. The study group consisted of 165 boys and 135 girls. The study included radiographs of patients of Polish nationality, aged 6-10 years, without diagnosed systemic diseases and local disorders. The study resulted in a set of original indicators to accurately assess the development of the second premolar tooth using computer image analysis and neural modelling. Five neural networks were generated, whose test quality was between 68-91%. The network dedicated to all quadrants of the dentition showed the highest test quality at 91%. The training, validation and test subsets were divided in a standard 2:1;1 ratio into 150 training cases, 75 test cases and 75 validation cases.

Non-syndromic tooth agenesis (ns-TA) is one of the most common dental anomalies characterized by the congenital absence of at least one permanent tooth (excluding third molars). Regarding the essential role of genetic factors in ns-TA aetiology, the present study aimed to identify novel pathogenic variants underlying hypodontia and oligodontia. In a group of 65 ns-TA patients and 127 healthy individuals from the genetically homogenous Polish population, the coding sequences of 423 candidate genes were screened using targeted next-generation sequencing. Pathogenic and likely pathogenic variants were identified in 37 (56.92%) patients, including eight nucleotide alternations of genes not previously implicated in ns-TA ( CHD7 , CREBBP , EVC , LEF1 , ROR2 , TBX22 and TP63 ). However, since only single variants were detected, future research is required to confirm and fully understand their role in the aetiology of ns-TA. Additionally, our results support the importance of already known ns-TA candidate genes ( AXIN2 , EDA , EDAR , IRF6 , LAMA3 , LRP6 , MSX1 , PAX9 and WNT10A ) and provide additional evidence that ns-TA might be an oligogenic condition involving the cumulative effect of rare variants in two or more distinct genes., Competing Interests: The authors declare no conflict of interest.

For non-syndromic cleft lip with or without cleft palate (ns-CL/P), the proportion of heritability explained by the known risk loci is estimated to be about 30% and is captured mainly by common variants identified in genome-wide association studies. To contribute to the explanation of the "missing heritability" problem for orofacial clefts, a candidate gene approach was taken to investigate the potential role of rare and private variants in the ns-CL/P risk. Using the next-generation sequencing technology, the coding sequence of a set of 423 candidate genes was analysed in 135 patients from the Polish population. After stringent multistage filtering, 37 rare coding and splicing variants of 28 genes were identified. 35% of these genetic alternations that may play a role of genetic modifiers influencing an individual's risk were detected in genes not previously associated with the ns-CL/P susceptibility, including COL11A1, COL17A1, DLX1, EFTUD2, FGF4, FGF8, FLNB, JAG1, NOTCH2, SHH, WNT5A and WNT9A. Significant enrichment of rare alleles in ns-CL/P patients compared with controls was also demonstrated for ARHGAP29, CHD7, COL17A1, FGF12, GAD1 and SATB2. In addition, analysis of panoramic radiographs of patients with identified predisposing variants may support the hypothesis of a common genetic link between orofacial clefts and dental abnormalities. In conclusion, our study has confirmed that rare coding variants might contribute to the genetic architecture of ns-CL/P. Since only single predisposing variants were identified in novel cleft susceptibility genes, future research will be required to confirm and fully understand their role in the aetiology of ns-CL/P., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Eruption is a complex and dynamic process determined by both genetic and epigenetic factors. This process involves a number of changes in the tissues surrounding the tooth and in tooth morphology. The aim of this study was to analyze the eruption sequence of permanent canines and premolars on the basis of pantomographic images. The study material consisted of 300 digital pantomographic images of children in the developmental period. The study group consisted of 165 boys and 135 girls. Images of patients of Polish nationality, aged 6-10 years, without diagnosed systemic diseases and local disorders were used in the study. Results: The study has shown that the most common pattern of tooth eruption in the lateral zones is type A positioning of the lateral teeth, which is 4-5-3. This pattern is characteristic of both girls and boys. This pattern also occurs most frequently in the maxilla in both boys and girls. In the mandible, on the contrary, two patterns of lateral tooth eruption were predominant. In girls, types A and E/4-5-3 and 3-4-5/occurred in the mandible, while in boys, types A and C/4-5-3 and 5-4-3/were observed in the mandible. The process of tooth eruption is a recognized measure of a child's physical development, and pantomographic images are an effective and common diagnostic tool.

Orthodontic retention is the final important stage of orthodontic treatment, the aim of which is to consolidate the functional and aesthetic position of teeth. Among adults, fixed retainers made of different types of wires are the most common. The aim of this study was to analyse the mechanical properties of a new generation of fixed orthodontic retainers-printed by 3D printers., Materials and Methods: The study was conducted using samples made of Nextdent MFH C&B N1 resin in the form of cuboid bars with nominal dimensions of width b = 3 mm, thickness d = 0.8 mm; 1 mm; 1.2 mm, length l = 30 mm for each type. The influence of the thickness of the retainers on their strength under loaded conditions was evaluated. Flexural strength, elastic properties, deflection, and creep were compared. The samples were aged in an artificial saliva bath at 37 ± 1 °C during the strength tests., Results: It was shown that differences in the thickness of the samples affected their elastic and strength properties. The highest average flexural modulus, the highest deflection, creep, and strength was characteristic of the samples with the highest thickness (1.2 mm). Samples with an average thickness of 1 mm had the lowest modulus of elasticity., Conclusions: The mechanical properties of 3D printed retainers show that they can be an alternative to metal retainers and the procedure of making new retainers, especially when patients have aesthetic requirements or allergies to metals.

Determining the chronological age of children or adolescents is becoming an extremely necessary and important issue. Correct age-assessment methods are especially important in the process of international adoption and in the case of immigrants without valid documents confirming their identity. It is well known that traditional, analog methods widely used in clinical evaluation are burdened with a high error rate and are characterized by low accuracy. On the other hand, new digital approaches appear in medicine more and more often, which allow the increase of the accuracy of these estimates, and thus equip doctors with a tool for reliable estimation of the chronological age of children and adolescents. In this study, the work on a fast and effective metamodel is continued. Metamodels have one great advantage over all other analog and quasidigital methods-if they are well trained, a priori, on a representative set of samples, then in the age-assessment phase, results are obtained in a fraction of a second and with little error (reduced to ±7.5 months). In the here-proposed method, the standard deviation for each estimate is additionally obtained, which allows the assessment of the certainty of each result. In this study, 619 pantomographic photos of 619 patients (296 girls and 323 boys) of different ages were used. In the numerical procedure, on the other hand, a metamodel based on the Proper Orthogonal Decomposition (POD) and Gaussian processes (GP) were utilized. The accuracy of the trained model was up to 95%.

Dental age is one of the most reliable methods for determining a patient's age. The timing of teething, the period of tooth replacement, or the degree of tooth attrition is an important diagnostic factor in the assessment of an individual's developmental age. It is used in orthodontics, pediatric dentistry, endocrinology, forensic medicine, and pathomorphology, but also in scenarios regarding international adoptions and illegal immigrants. The methods used to date are time-consuming and not very precise. For this reason, artificial intelligence methods are increasingly used to estimate the age of a patient. The present work is a continuation of the work of Zaborowicz et al. In the presented research, a set of 21 original indicators was used to create deep neural network models. The aim of this study was to verify the ability to generate a more accurate deep neural network model compared to models produced previously. The quality parameters of the produced models were as follows. The MAE error of the produced models, depending on the learning set used, was between 2.34 and 4.61 months, while the RMSE error was between 5.58 and 7.49 months. The correlation coefficient R 2 ranged from 0.92 to 0.96.

The analog methods used in the clinical assessment of the patient's chronological age are subjective and characterized by low accuracy. When using those methods, there is a noticeable discrepancy between the chronological age and the age estimated based on relevant scientific studies. Innovations in the field of information technology are increasingly used in medicine, with particular emphasis on artificial intelligence methods. The paper presents research aimed at developing a new, effective methodology for the assessment of the chronological age using modern IT methods. In this paper, a study was conducted to determine the features of pantomographic images that support the determination of metric age, and neural models were produced to support the process of identifying the age of children and adolescents. The whole conducted work was a new methodology of metric age assessment. The result of the conducted study is a set of 21 original indicators necessary for the assessment of the chronological age with the use of computer image analysis and neural modelling, as well as three non-linear models of radial basis function networks (RBF), whose accuracy ranges from 96 to 99%. The result of the research are three neural models that determine the chronological age.

With easy-to-process 3D printing materials and fast production, the quality of dental services can be improved. In the conventional procedure, the dentist makes temporary crowns directly in the patient's mouth, e.g., from the most commonly used bis-acrylic composites. Temporary crowns made directly in the office without the use of CAD/CAM are often of inferior quality, which directly results in impaired hygiene, poorer masticatory mechanics, greater deposition of plaque, calculus and sediment, and may adversely affect periodontal and gum health. The mechanical strength, resistance to aging and abrasion of 3D printing materials are higher than those of the soft materials used in conventional methods. This translates into durability. The patient leaves the surgery with a restoration of higher utility quality compared to the conventional method. The objective of the paper was to determine the influence of aging in artificial saliva of AM (additive manufacturing) orthodontic composites on their functional properties. For the purpose of the study, fillings well-known worldwide were selected. These were traditional UV-curable resins (M I, M II, M III, M V) and a hybrid material based on a UV-curable resin (M VI). Samples were stored in artificial saliva at 37 ± 1 °C in a thermal chamber for 6 months. Indentation hardness, frictional tests and sliding wear measurements were conducted. A comparison between various materials was made. Descriptive statistics, degradation coefficients, H 2 E, Archard wear and specific wear rate were calculated. The Weibull statistical test for indentation hardness was performed and Hertzian contact stresses for the frictional association were calculated for unaged (M I, M II, M III, M V, M VI) and aged (M I AS, M II AS, M III AS, M V AS, M VI AS) samples. M I exhibited the lowest average hardness among the unaged materials, while M III AS had the lowest average hardness among the aged materials. Comparably low hardness was demonstrated by the M I AS material. The coefficient of friction values for the aged samples were found to be higher. The lowest wear value was demonstrated by the M I material. The wear resistance of most of the tested materials deteriorated after aging. The M VI AS material had the highest increase in wear. According to the results provided, not only the chemical composition and structure, but also aging have a great impact on the indentation hardness and wear resistance of the tested orthodontic materials.

Background: Clinical success depends on the contact strength and wear resistance of medical devices made of polymer materials. The scientific goal resulted from the problem of using different methods of surface evaluation of materials used in the production of orthodontic appliances. The purpose of the work was an experimental comparative assessment of indentation hardness and scratch hardness and the sliding wear of four selected polymeric materials used in the manufacture of orthodontic appliances., Methods: Four commercial materials were compared. Shore hardness tests and a scratch test with a Rockwell indenter were performed. A sliding wear test was performed using the ball-on-disc method. Statistical PCA and correlation analyses were performed., Results: The results of scratch hardness measurements using a contact profilometer correlated with the Shore hardness to a greater extent than measurements made using an optical microscope. PCA showed that Shore hardness explains 45% of the total variance in all the results across the materials., Conclusions: The scratch hardness method allows for a more explicit ranking of orthodontic polymeric materials when measurements are made with a profilometer. The ranking of sliding wear resistance should be made separately.

This paper discusses the issues of strength and creep of polymeric materials used in orthodontic appliances. Orthodontic biomechanics is focused on the movement of individual teeth or dental groups as a result of the force applied by orthodontic appliances. Stresses in the construction of functional and biomechanical appliances is generated when using the apparatus in the oral cavity. The orthodontic appliance must maintain its shape and not be damaged during treatment so strength and creep resistance are fundamental properties. It was assumed that the clinical success of orthodontic appliances can be determined by these performance properties. The aim of the work was the experimental assessment of comparative bending strength and creep resistance of selected popular polymer materials used in the production of biomechanical orthodontic appliances. Four commercial materials manufactured by the world class producers were tested: NextDent Ortho Rigid (Vertex-Dental B.V., Soesterberg, The Netherlands) marked as "1A"; Erkocryl (ERKODENT Erich Kopp GmbH, Pfalzgrafenweiler, Germany)-"2A"; Vertex Orthoplast (Vertex Dental B.V.), blue, marked as "3A" and material with the same name as "3A" but orange, marked in the article as "4A". All the tests were carried out after aging in artificial saliva for 48 h at a temperature of 37 °C. Flexular strength and flexular modulus were made using the three point bending method according to the ISO 178 technical standard. Creep tests were carried out according to the method contained in ISO 899-2. The creep test was carried out in an artificial saliva bath at 37 °C. The creep tests showed significant differences in the strength, modulus and deformability of the tested materials. The strength reliability of the tested materials also varied. The research shows that the 2A material can be used for orthodontic applications in which long-term stresses should be lower than 20 MPa.

The cosmetic and pharmaceutical industry is constantly on the lookout for new and efficient active substances. In this article, we focus on resveratrol, an active substance with beneficial health properties, which is obtained, among others, from vines and knotweed (Reynoutria japonica). In this study, we assessed the level of skin hydration in a group of probands who used cream with or without resveratrol. The compound has been shown to have moisturizing and tightening properties, improving the overall condition of the skin.

Objective: The etiology of non-syndromic cleft lip with or without cleft palate (nsCL/P) is multifactorial, heterogeneous, and still not completely understood. The aim of the present study was to examine the associations between common and rare PAX7 nucleotide variants and the risk of this common congenital anomaly in a Polish population., Subjects and Methods: Eight top nsCL/P-associated PAX7 variants identified in our cleft genome-wide association study (GWAS) were selected for replication analysis in an independent group of patients and controls (n = 247 and n = 445, respectively). In addition, mutation screening of the PAX7 protein-coding region was conducted., Results: Analysis of the pooled data from the GWAS and replication study confirmed that common PAX7 nucleotide variants are significantly associated with the increased risk of nsCL/P. The strongest individual variant was rs1339062 (c.586 + 15617T > C) with a p-value = 2.47E-05 (OR = 1.4, 95%CI: 1.20-1.64). Sequencing analysis identified a novel synonymous PAX7 substitution (c.87G > A, p.Val29Val) in a single patient with nsCLP. This transition located in the early exonic position was predicted to disrupt potential splice enhancer elements., Conclusion: Our study confirmed that PAX7 is a strong candidate gene for nsCL/P. Nucleotide variants of this gene contribute to the etiology of nsCL/P in the homogenous Polish population., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Although the aetiology of non-syndromic cleft lip with or without cleft palate (nsCL/P) has been studied extensively, knowledge regarding the role of genetic factors in the pathogenesis of this common craniofacial anomaly is still limited. We conducted a follow-up association study to confirm that CDKAL1 nucleotide variants identified in our genome-wide association study (GWAS) for nsCL/P are associated with the risk of this anomaly. In addition, we performed a sequence analysis of the selected CDKAL1 exons. A mega-analysis of the pooled individual data from the GWAS and a replication study revealed that six out of thirteen CDKAL1 variants were positively replicated and reached the threshold of statistical significance (P trend  < 3.85E-03). They represented a single association signal and were located within the fifth intron of CDKAL1. The strongest individual variant was rs9356746 with a P trend value = 5.71E-06 (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.30-1.97). Sequencing analysis did not reveal any pathogenic mutations of this gene. This study provides the first evidence that chromosomal region 6p22.3 is a novel susceptibility locus for nsCL/P. The location of the risk variants within the CDKAL1 intronic sequence containing enhancer elements predicted to regulate the SOX4 transcription may suggest that SOX4, rather than CDKAL1, is a potential candidate gene for this craniofacial anomaly.

Background: The loss of physical properties of orthodontic chains has been a topic of discussion among scientists and clinicians, motivating efforts to improve elastic materials and minimize the decrease of force. Orthodontic companies have introduced memory elastomers, which, according to the manufacturers, have improved mechanical properties., Objectives: The aim of the study was to evaluate the effects of stretching elastomeric chains submerged in 37°C artificial saliva., Material and Methods: The study assessed 2 types of chains. The first phase of the study evaluated 1) the tensile strength of the chains; and 2) elongation at the time of tearing in an environment outside of the oral cavity (without exposition). The second phase of the study evaluated 1) permanent deformation after stretching; 2) elongation at the time of tearing; and 3) the tensile strength of the chain in conditions similar to those present in the oral cavity., Results: In the experiments using artificial saliva, pronounced force decay was observed in the plastic chain, in which, after just 7 days, force decreased almost by half compared to the initial value, with a continuous downward trend. The memory chain, however, showed increased elasticity, and after the first week of exposition the force decay at the time of tearing was around 20% of the initial value. Force decay at the time of tearing remained at a steady level between 14.4 and 25.4% throughout the whole period of exposition. In the plastic chain this value oscillated between 50.3 and 55.9%. In the experiments assessing permanent deformation of the chains performed after each week of exposition, the specimens prepared from the memory chain stretched from 8 cm to approximately 9.5 cm after exposition, while the specimens prepared from the plastic chain stretched to approximately 13 cm., Conclusions: Memory chains are more effective in orthodontic treatment due to diminished loss of mechanical and elastic capabilities, when compared to plastic chains.

Congenital maxillary lateral incisor agenesis (MLIA) is one of the most common subtypes of dental agenesis. Because little is known with regard to the aetiology of this anomaly, the aim of the study was to determine the contribution of nucleotide variants in wingless-type MMTV integration site family, member 10A (WNT10A), msh homeobox 1 (MSX1), and paired box 9 (PAX9) to the risk of MLIA in a Polish population. Coding regions of the selected genes were analysed by direct sequencing in a group of 20 individuals with unilateral and bilateral MLIA, associated or not with other dental anomalies. The frequencies of the identified nucleotide variants were assessed in an additional cohort of patients with isolated dental agenesis (n = 147) and in 178 controls. Mutation screening showed four non-synonymous substitutions located in the highly conserved coding sequence of WNT10A in five (25%) of the 20 patients. Analysis of genotyping results revealed that three of these variants--p.Arg113Cys, p.Phe228Ile, and the newly identified p.Arg171Leu--may represent aetiological mutations underlying MLIA with associated dental anomalies. No mutations that were potentially aetiologic were identified in MSX1 and PAX9. In conclusion, this is the first report implicating coding variants in the WNT10A gene in the aetiology of MLIA. These results will require further confirmation using larger-scale studies., (© 2014 Eur J Oral Sci.)

Objective: Tooth agenesis is the most common developmental anomaly of the human dentition, with aetiology involving both genetic and environmental factors. The aim of the study was to search for casual mutations underlying hypodontia in a family with agenesis of the second premolars and third molars., Design: Direct sequencing of the coding regions including exon-intron boundaries of the MSX1 and PAX9 genes was performed in all affected family members., Results: Novel heterozygous mutation segregating in an autosomal dominant model was identified in the MSX1 gene. This c.T671C transition leads to a substitution of leucine by proline at position 224, which is the penultimate amino acid residue of the highly conserved homeodomain. None of the control subjects (600 chromosomes) were carriers of this novel, probably damaging to protein function, mutation., Conclusions: Our results demonstrate for the first time that MSX1 might play a substantial role in familial cases of hypodontia involving only second premolars and third molars. The novel c.T671C mutation might be the etiological variant of the MSX1 gene responsible for the lack of permanent teeth in the tested family., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The wingless-type MMTV integration site family (Wnt) signalling pathway plays a crucial role in craniofacial development. Recently, nucleotide variants in WNT genes have been shown to be associated with oral congenital anomalies, including facial clefts. Therefore, in the current study we decided to assay the association of nucleotide variants in selected WNT genes with the risk of non-syndromic cleft lip with or without cleft palate (NCL/P) in the Polish population. Fourteen polymorphisms in WNT3, WNT3A, WNT5A, WNT8A, WNT9B, and WNT11 were tested in a group of 210 patients with NCL/P and in a properly matched control group. The most significant results were found for the WNT3 rs3809857 variant, which, under the assumption of a recessive model, was associated with a two-fold decrease in the risk of NCL/P (OR(TT vs. GT + GG) = 0.492, 95% CI: 0.276-0.879, P = 0.015). Moreover, haplotype analysis revealed that WNT3 is significantly correlated with NCL/P. The global P-values for haplotypes of rs12452064&#95;rs7207916 and rs3809857&#95;rs12452064&#95;rs7207916 were 0.0034 and 0.0014, respectively, and these results were statistically significant, even after the permutation test correction. In conclusion, our study confirmed the involvement of polymorphisms in the WNT3 gene in NCL/P aetiology in the tested population., (© 2012 Eur J Oral Sci.)

Background: Non-syndromic cleft lip and palate (CLP) is one of the most common birth defects. Recent genome-wide association studies (GWAS) have identified several novel risk loci associated with this craniofacial anomaly. Therefore, the objective of this report was to investigate the contribution of the top seven polymorphisms reaching genome-wide statistical significance in GWAS analyses in the Polish population., Methods and Results: Nucleotide variants located at chromosomal regions 1p22.1, 10q25.3, 17q22, and 20q12 were tested in a group of 206 patients with nonsyndromic CLP and a properly matched control group. Significant results, which persisted even after Bonferroni correction (p < 0.0071), were observed for polymorphisms located at 10q25.3 (rs7078160 and rs4752028) and 17q22 (rs227731). Under a recessive model, both rs7078160 and rs4752028 were associated with a greater than fourfold increase in the risk of CLP (odds ratio [OR] = 4.536; 95% confidence interval [CI], 1.678-12.265; p = 0.0012 and OR = 4.573; 95% CI, 1.817-11.512; p = 0.0004, respectively). Polymorphism rs227731 increased the risk of CLP when analyzed under a dominant model (OR = 1.732; 95% CI, 0.184-2.253; p = 0.0044). Borderline association was alsoidentified for the 1p22.1 locus (rs481931). Moreover, 10q25.3 haplotypes were significantly associated with a susceptibility to CLP., Conclusion: Our evaluation study confirmed a substantial association of polymorphisms located at chromosomal regions 10q25.3 and 17q22 with nonsyndromic CLP in the Polish population., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Tooth agenesis is one of the most common anomalies of human dentition and is due to a complex and not fully elucidated etiology. The purpose of this study was to evaluate the possibility that polymorphic variants of genes encoding the main folate and choline metabolism enzymes might be associated with the risk of hypodontia in the Polish population., Methods and Results: We analyzed 21 polymorphisms of 13 candidate genes and found that single nucleotide polymorphisms (SNPs) in the CHDH gene are significantly correlated with the risk of dental agenesis. The strongest association was found for the SNP located in the intronic sequence of CHDH. Individuals carrying one copy of the rs6445606 C allele had an over two-fold decreased risk of having hypodontia (odds ratio [OR]CTvsTT=0.434; 95% confidence interval [CI], 0.2724-0.6915; p=0.0004; pcorr=0.0084). A reduced risk of tooth agenesis was also observed in individuals with one or two copies of the rs6445606 C allele compared to T allele carriers (ORCT+CCvsTT=0.524; 95% CI, 0.3386-0.8097; p=0.0035; pcorr=0.0735). Moreover, the gene-gene interaction analysis revealed a significant epistatic interaction between CHDH (rs6445606) and PLD2 (rs3764897) in the susceptibility to hypodontia (p=0.004)., Conclusion: Our study identified CHDH and PLD2 as novel candidate genes, the nucleotide variants of which could be associated with the risk of tooth agenesis., (Copyright © 2011 Wiley-Liss, Inc.)

Nonsyndromic cleft lip with or without cleft palate (NCL/P) is one of the most common craniofacial malformations; however, its aetiology is still unclear. Because the effects of maternal nutrition on fetal development are well known, we decided to pursue the question of whether polymorphic variants of genes encoding enzymes involved in choline metabolism might be associated with the maternal risk of having a baby with NCL/P. Analysis of 18 single nucleotide polymorphisms (SNPs) of betaine-homocysteine methyltransferase (BHMT), betaine-homocysteine methyltransferase-2 (BHMT2), choline dehydrogenase (CHDH), choline kinase (CHKA), dimethylglycine dehydrogenase (DMGDH), choline-phosphate cytidylyltransferase A (PCYT1A), and phosphatidylethanolamine N-methyltransferase (PEMT) provided evidence that polymorphisms located in the region containing BHMT and BHMT2 were protective factors against NCL/P affected pregnancies in our population. The strongest signal was found for the SNP located in the intronic sequence of BHMT2. Women carrying two copies of the rs625879 T allele had a significantly decreased risk of having offspring with orofacial clefts. These results were significant, even after correction for multiple comparisons. Moreover, the gene-gene interaction analysis revealed a significant epistatic interaction of BHMT2 (rs673752), PEMT (rs12325817), and PCYT1A (rs712012) with maternal NCL/P susceptibility. Altogether, our study identified a novel gene, the nucleotide variants of which were be associated with a decreased risk of having a baby with NCL/P., ((c) 2010 The Authors. Journal compilation (c) 2010 Eur J Oral Sci.)

Background: Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population., Methods: We performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFalpha, TGFbeta3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group., Results: Highly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio [OR](AG+AAvsGG), 1.635; 95% confidence interval [CI], 1.153-2.319; p = 0.005; and OR(AC+AAvsCC), 1.962; 95% CI, 1.382-2.785; p = 1.4 x 10(-4), respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; OR(CGvsGG), 1.580; 95% CI, 1.056-2.363; p = 0.025)., Conclusions: Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample., (2010 Wiley-Liss, Inc.)

PAX9 is a paired domain transcription factor that plays a critical role in odontogenesis. All mutations of PAX9 identified to date have been associated with nonsyndromic form of tooth agenesis. The present report describes an unusual novel mutation in PAX9 identified in a family with severe molar oligodontia. This heterozygous deletion combined with 24 bp insertion (including a 5' splice site) is localized in the second exon beyond the highly conserved paired box sequence, and might result either in a premature termination of translation at aa 210 or in an aberrant splicing, leading to a frameshift and premature termination of translation at aa 314. Real-time PCR analysis revealed no mutated transcript in cultured lymphocytes of one of the affected individuals indicating that the novel mutation might result in rapid degradation of the mutated transcript leading to haploinsufficiency of PAX9. Our results support the view that mutations in PAX9 constitute a causative factor in nonsyndromic oligodontia.

Selective tooth agenesis is the most common developmental abnormality of the human dentition. To date, this abnormality has been associated only with mutations in MSX1 and PAX9 mutations, however it has recently been suggested that mutations of axis inhibition protein 2 (AXIN2) may also contribute to this complex anomaly. The protein product of this gene is a negative regulator of the Wnt-signaling pathway. We searched for AXIN2 variants in a group of patients with tooth agenesis who did not have mutations of MSX1 and PAX9. Using multi-temperature single-stranded conformational polymorphism and sequencing analysis, we identified three novel AXIN2 gene variants: c.956+16A > G, c.1060-17C > T and c.2062C > T. We also observed that individuals carrying the c.956+16G and c.2062T alleles exhibited an increased risk of tooth agenesis. The calculated odds ratio was 2.94 (95% CI 1.104-7.816; p = 0.026; p(corr) = 0.234) and 4.01 (95% CI 1.563-10.301; p = 0.002; p(corr) = 0.018), respectively. Moreover, we found that the c.2062C > T transition may change exon splice enhancer-specific binding sites of the protein splicing regulators SC35 and SF2/ASF. This alternation may negatively affect the splicing process and cellular concentration of AXIN2 protein. Our findings suggest that AXIN2 polymorphic variants may be associated with both hypodontia and oligodontia.

Even though selective tooth agenesis is the most common developmental anomaly of human dentition, its genetic background still remains poorly understood. To date, familial as well as sporadic forms of both hypodontia and oligodontia have been associated with mutations or polymorphisms of MSX1, PAX9, AXIN2 and TGFa, whose protein products play a crucial role in odontogenesis. In the present report we described a novel mutation of MSX1, which might be responsible for the lack of 14 permanent teeth in our proband. However, this c.581C>T transition, localized in a highly conserved homeobox sequence of MSX1, was identified also in 2 healthy individuals from the proband's family. Our finding suggests that this transition might be the first described mutation of MSX1 that might be responsible for oligodontia and showing incomplete penetrance. It may also support the view that this common anomaly of human dentition might be an oligogenic trait caused by simultaneous mutations of different genes.

Tooth development is regulated through a series of reciprocal interactions between the dental epithelium and mesenchyme and requires protein products of a number of genes. It has been reported that selective tooth agenesis is associated with mutations in human MSX and PAX9 genes. Mutational analysis of the two genes was performed in 25 individuals with familial or sporadic form of permanent tooth agenesis. Single-stranded conformational polymorphism analysis revealed no mutations in the entire coding sequence of the MSX1 gene. In PAX9, a novel, heterozygous G151A transition in the sequence encoding the paired domain of the PAX9 protein was detected in a patient with agenesis of third molars, second premolars and incisors, but not in her parents, the remaining patients or 162 individuals with normal dentition. This is the first de novo mutation described in PAX9. Our results support the view that mutations in PAX9 could constitute a causative factor of oligodontia. We hypothesize that the G151A transition in PAX9 might be responsible for the sporadic form of tooth agenesis in this patient.

The structure of the EDA1 gene was investigated in a patient with anhidrotic ectodermal dysplasia. Sequence analysis revealed a novel A1270G transition in exon 9 of the EDA1 gene in the patient and his uncle, whereas the patient's mother and grandmother were heterozygotes. This mutation resulted in Tyr343Cys substitution in the extracellular domain of the EDA1 gene product - ectodysplasin-A. The additional Cys343 was located between Cys332 and Cys346 and formed with Cys352 a cluster of four closely situated residues that could potentially form disulfide bonds. This mutation might affect the tertiary structure of the receptor-binding domain of ectodysplasin-A and precipitate the clinical symptoms of anhidrotic ectodermal dysplasia.