Morphological and Dimensional Analysis of the Nasopalatine Canal: Insights from Cone-Beam Computed Tomography Imaging in a Large Cohort.

BACKGROUND The nasopalatine canal (NPC), or incisive canal, is located in the midline of the palate, posterior to the maxillary central incisors. Its anatomy is important in prosthetic dentistry procedures. This study aimed to assess the anatomical morphology of the NPC according to age, sex, and dental status using cone-beam computed tomography (CBCT) in 335 patients. MATERIAL AND METHODS In this retrospective cross-sectional study, a total of 335 patients were recruited and categorized according to sex, age, and dental status. Individual CBCT images were analyzed in the sagittal, coronal, and axial planes. Also, we recorded the dimensions and morphological shape of the NPC and adjacent buccal bone plate (BBP) under standardized conditions. The associations between sex, age group, NPC shapes and types, and presence of central incisors were assessed. A significance level was set at P<0.05. RESULTS Mean labio-palatal and mediolateral measurements of the incisive foramen were 5.13±1.45 mm and 3.21±0.96 mm, whereas the mean diameter of Stenson foramen was 2.57±1.25 mm, and the total length of the NPC was 11.79±2.50 mm. Funnel, Y, and round-shaped canals were the most prevalent shapes of the NPC in sagittal, coronal, and axial planes. BBP was greater in men, with P=0.011, P=0.000, and P=0.001 at BBP1, BBP2, and BBP3, respectively. CONCLUSIONS NPC and BBP parameter values were slightly higher among male patients. NPC parameters increased with older age. The crest width of BBP decreased with older age and after missing maxillary central incisor teeth.

High Prevalence of Musculoskeletal Disorders Among Dental Professionals: A Study on Ergonomics and Workload in Yemen.

BACKGROUND Dentists frequently have work-related musculoskeletal disorder (MSD) diseases, which are the profession's second most common cause of disability. Awareness of dental ergonomics is necessary for controlling MSDs associated with dental workload. Dental professionals need additional training in dental ergonomics to reduce serious complications associated with dental workload. This questionnaire-based study aimed to evaluate the understanding of physical ergonomics and musculoskeletal disorders in 310 dental health professionals and students in Yemen. MATERIAL AND METHODS This was a cross-sectional study was conducted among 400 dental professionals working in various clinics and universities in Sana'a City, Yemen. They received a self-administered questionnaire that was developed from earlier studies. Five sections made up the questionnaire. The first section of the survey included questions about sex, age, and clinical professions; the second section focused on ergonomic awareness; the third section asked about work conditions; the fourth section asked about the prevalence of musculoskeletal disorders; and the fifth section asked about interventions used. Data were analyzed using SPSS version 25.0, and a P value of ≤0.05 was considered significant. RESULTS Only 310 questionnaires were completed. The participants'; level of understanding of ergonomics was low. One-way ANOVA showed a significant portion of respondents reported having MSDs, and they frequently reported pain related to workload. The neck, lower back, upper back, and shoulders experienced the highest levels of pain. CONCLUSIONS The prevalence of MSDs was high among dental professionals, especially in the lower back, upper back, and shoulder. This necessitates preventive measures like ergonomic positions, ergonomic equipment, regular exercise, and work breaks.

Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores.

BACKGROUND: Nonsyndromic cleft lip with/without cleft palate (nsCL/P) is a congenital malformation of multifactorial etiology. Research has identified >40 genome-wide significant risk loci, which explain less than 40% of nsCL/P heritability. Studies show that some of the hidden heritability is explained by rare penetrant variants. METHODS: To identify new candidate genes, we searched for highly penetrant de novo variants (DNVs) in 50 nsCL/P patient/parent-trios with a low polygenic risk for the phenotype (discovery). We prioritized DNV-carrying candidate genes from the discovery for resequencing in independent cohorts of 1010 nsCL/P patients of diverse ethnicities and 1574 population-matched controls (replication). Segregation analyses and rare variant association in the replication cohort, in combination with additional data (genome-wide association data, expression, protein-protein-interactions), were used for final prioritization. CONCLUSION: In the discovery step, 60 DNVs were identified in 60 genes, including a variant in the established nsCL/P risk gene CDH1. Re-sequencing of 32 prioritized genes led to the identification of 373 rare, likely pathogenic variants. Finally, MDN1 and PAXIP1 were prioritized as top candidates. Our findings demonstrate that DNV detection, including polygenic risk score analysis, is a powerful tool for identifying nsCL/P candidate genes, which can also be applied to other multifactorial congenital malformations.

Epidemiology of Facial Profiles, Occlusal Features, and Orthodontic Treatment Need among Adolescence: A Cross-sectional Study.

AIMS: This study aimed to investigate the incidence and severity of malocclusion and orthodontic treatment needs among randomly selected high school students. METHODS: A multistage stratified random-sampling study was conducted on 1,036 high school students in Sana'a city. The World Dental Federation and World Health Organization method of occlusal traits and the index of orthodontic treatment need were adopted for measurements. Clinically, the molar relationship and facial profile were examined. Assessment of whether examiner or subject perceived the need for orthodontic treatment was made using the esthetic component index. All data were analyzed using the Chi-square test with a significance level of p <0.05. RESULTS: Normal, convex, and concave facial-profile measurements were found in 81.9, 12.1, and 6.15% of sampled students, respectively. Asymmetrical molar relationship was observed in 16.1% of samples, and most of them were of class I/class II relationships. Increased overjet was noticed in 90.9% of students. Anterior crossbite, deepbite, anterior openbite, posterior openbite, posterior crossbite, and scissor bite accounted for 12.2, 12.8, 3.5, 1.3, 6.6, and 0.6%, respectively. According to the index orthodontic treatment need, 38.9% of students needed some form of orthodontic treatment. Among these cases, 24.3% "definitely" needed treatment, and 59.9% of students needed orthodontic treatment. CONCLUSION: Our findings suggested a call for a more conservative treatment approach in dealing with malocclusion problems among high school students in all zones of Sana'a governorate, Yemen. CLINICAL SIGNIFICANCE: A limited number of surveys were performed in Sana'a Governorate to investigate orthodontic treatment needs, facial profiles, and occlusal features among adolescents. The results of this study could guide us to develop a preventive system that minimizes its adverse effects and the need for costly orthodontic treatments.

Predictive factors associated with adjacent teeth root resorption of palatally impacted canines in Arabian population: a cone-beam computed tomography analysis.

BACKGROUND: This study aimed to evaluate three-dimensionally the factors associated with adjacent teeth root resorption of palatally impacted canines. METHODS: In this retrospective cross-sectional study, one-hundred and fourteen cone beam computed tomography scans with palatally impacted maxillary canines were evaluated for the presence of adjacent root resorption. Seven parameters were analyzed: alignment of maxillary incisors, presence of deciduous canines, first premolars' roots configuration, impacted canines rotation, angulation of impacted canine to the midline, contact relationship, and area of contact with adjacent teeth. The association between dependent and independent qualitative and quantitative variables was analyzed using chi-square and independent student's t-test, respectively. The multivariate analysis was performed using regression analysis. The significant value was set at P ≤ 0.05. RESULTS: The overall incidence of vertical, horizontal impaction and adjacent root resorption were 92, 8 and 77.2%, respectively. The apical third was the most involved area (57%); resorption of a single tooth was found in 21.9% of the total sample. The most common resorbed teeth were lateral first premolars (24.6%), followed by central lateral incisors (20.2%), and lateral incisors (15.8%) of the total sample. The severity of resorption was highest in grade I (31.5%) and lowest in grade III (7.6%). Three variables showed significant differences between resorption and non-resorption groups namely; canine rotation (P < 0.013), contact relationship (P < 0.001), and area of contact with adjacent teeth (P < 0.001). Regression analysis revealed an association between adjacent root resorption and permanent canine rotation, adjacent premolars' roots configuration, contact relationship, and area of contact (P < 0.05). CONCLUSION: Two-thirds of impacted maxillary canines showed a form of root resorption. The most commonly resorbed tooth was the lateral incisors while the least affected one was the central incisors with apical one-third being of the highest risk. The predisposing factors including the canine rotation, premolar with separated roots, contact relationship, and area of contact with adjacent teeth are to be considered for any interceptive treatment.

Short Versions of the Arabic Psychosocial Impact of Dental Aesthetics Questionnaire for Yemeni Adolescents: Cross-Sectional Derivation and Validation.

Objectives: To shorten the 24-item Arabic Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ(A)) for adolescents in Yemen. Material and methods: Two shortening methods derived six-item and nine-item versions: the item impact method selected items with the highest impact scores as rated by 30 participants in each subscale; and the regression method was applied using data of 385 participants from the PIDAQ(A) validity study, with the total PIDAQ(A) score as the dependent variable, and its individual items as the independent variables. The four derived versions were assessed for validity and reliability. Results: The means of the six-item and nine-item short versions of both methods were close. Cronbach's alpha values extended from 0.90 to 0.92 (intra-class correlations = 0.85−0.88). In criterion validity, strong significant correlations were detected between scores of all short versions and the 24-item PIDAQ(A) score (0.96−0.98; p < 0.001). Construct validity displayed significant associations among all short versions and self-perceived dental appearance rank and self-perceived need for orthodontic braces rank (p < 0.05). Mean scores of all short versions were significantly different between adolescents with severe malocclusion and those with slight malocclusion in discriminant validity tests. In conclusion, all PIDAQ(A) short versions are valid and reliable.

Validity and Reliability of the Arabic Version of the Psychosocial Impact of Dental Aesthetics Questionnaire for Yemeni Adolescents.

(1) Objectives: This paper aimed to cross-culturally adapt the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) into an Arabic language version (PIDAQ(A)) for measuring the oral health related quality of life related to dental aesthetics among 12-17-year-old Yemeni adolescents. (2) Material and methods: The study comprised three parts, which were linguistic validation and qualitative interview, comprehensibility assessment, and psychometric validations. Psychometric properties were examined for validity (exploratory factor analysis (EFA), partial confirmatory factor analysis (PCFA), construct, criterion, and discriminant validity) and reliability (internal consistency and reproducibility). (3) Results: The PIDAQ(A) contained a new item. EFA extracted three factors (item factor loading 0.375 to 0.918) comprising dental self-confidence, aesthetic concern, and psychosocial impact subscales. PCFA showed good fit statistics (comparative fit index (CFI) = 0.928, root-mean-square error of approximation (RMSEA) = 0.071). In addition, invariance across age groups was tested. Cronbach's α values ranged from 0.90 to 0.93 (intraclass correlations = 0.89-0.96). A criterion validity test showed that the PIDAQ(A) had a significant association with oral impacts on daily performance scores. A construct validity test showed significant associations between PIDAQ(A) subscales and self-perceived dental appearance and self-perceived need for orthodontic braces (p < 0.05). Discriminant validity presented significant differences in the mean PIDAQ(A) scores between subjects having severe malocclusion and those with slight malocclusion. No floor or ceiling effects were detected.

Extending the allelic spectrum at noncoding risk loci of orofacial clefting.

Genome-wide association studies (GWAS) have generated unprecedented insights into the genetic etiology of orofacial clefting (OFC). The moderate effect sizes of associated noncoding risk variants and limited access to disease-relevant tissue represent considerable challenges for biological interpretation of genetic findings. As rare variants with stronger effect sizes are likely to also contribute to OFC, an alternative approach to delineate pathogenic mechanisms is to identify private mutations and/or an increased burden of rare variants in associated regions. This report describes a framework for targeted resequencing at selected noncoding risk loci contributing to nonsyndromic cleft lip with/without cleft palate (nsCL/P), the most frequent OFC subtype. Based on GWAS data, we selected three risk loci and identified candidate regulatory regions (CRRs) through the integration of credible SNP information, epigenetic data from relevant cells/tissues, and conservation scores. The CRRs (total 57 kb) were resequenced in a multiethnic study population (1061 patients; 1591 controls), using single-molecule molecular inversion probe technology. Combining evidence from in silico variant annotation, pedigree- and burden analyses, we identified 16 likely deleterious rare variants that represent new candidates for functional studies in nsCL/P. Our framework is scalable and represents a promising approach to the investigation of additional congenital malformations with multifactorial etiology.

Three-dimensional assessment of accelerating orthodontic tooth movement-micro-osteoperforations vs piezocision: A randomized, parallel-group and split-mouth controlled clinical trial.

OBJECTIVE: To compare the effects of micro-osteoperforations (MOPs) vs piezocision (Piezo) in accelerating orthodontic tooth movement in adults. SETTING AND SAMPLE POPULATION: In this randomized, single-blinded, parallel-group, split-mouth clinical trial, 24 patients aged 15-40 years were recruited. SUBJECTS AND METHODS: Patients were randomly allocated into two groups: MOPs and Piezo groups. One side of the maxilla was allocated randomly for treatment with one of these techniques, and the other side was treated conventionally to act as a split-mouth control. The rate of canine retraction was evaluated up to 3 months by three-dimensional digital models using a conventional labial appliance. Root resorption and bone height were evaluated using cone beam computed tomography. RESULTS: The MOPs and Piezo groups showed a significantly higher rate of tooth movement after 3 months on the experimental sides than the control sides. However, the net movements in the MOPs and Piezo groups did not reveal a higher rate of tooth movement. Similarly, the overall net movement was -0.32 ± 1.14 and -0.55 ± 0.89 mm for MOPs and Piezo, respectively (P = .606). Regarding root resorption, the overall changes in intra- or intergroup comparisons were insignificant. Decreased canine palatal bone height was reported on the experimental side of the Piezo group (P = .015) after 3 months, but the overall changes were insignificant. CONCLUSIONS: The effect of MOPs and Piezo techniques in accelerating the orthodontic canine retraction was comparable to each other, and to the conventional methods. Neither technique caused root resorption or increased vertical bone loss.

Perception of Dental Students and Laypersons to Altered Dentofacial Aesthetics.

AIMS AND OBJECTIVES: The aims of the study were to comprehensively assess the perception of altered dentofacial aesthetics between dental students and laypersons and to identify the threshold where different variables such gender and clinical training impair dentofacial attractiveness. MATERIALS AND METHODS: Ten photographs were digitally manipulated involving three facial, two smile, four dental, and one gingival components. Fifty images were randomized and rated according to attractiveness by two groups dental students which subdivided into preclinical students and clinical students, and laypersons. The participants evaluated the original and manipulated images using a visual analog scale. The responses were then analyzed using Mann-Whitney U test. RESULTS: The results showed threshold levels of noticeable differences between varying levels of discrepancy. The overall perception of aesthetics was high among dental clinical students with the highest perception toward facial profile and the lowest toward gingival margin height. Of the respondents, no differences were found in the perception between male and female participants. Dental students perceived aesthetic components more accurately than laypersons. CONCLUSION: Dental students group had a better perception of dentofacial aesthetics than included laypersons. Unlike gender, clinical training has a substantial positive effect on the assessment of beauty. Dental students sub divided into dental preclinical students and dental clinical students (clinical training is a variable of all subgroups).

Relationship between cervical vertebral maturation and dental development in a sample of yemeni children and adolescents / Relación entre la maduración vertebral cervical y el desarrollo dental en una muestra de niños y adolescentes yemeníes

Objective: This study was conducted to investigate the relationship between dental development and cervical vertebral maturation stages in a group of Yemeni children and adolescents. Materials an Methods: The study included digital panoramic radiographs and lateral skull cephalograms obtained from 207 Yemeni subjects­122 females and 85 males aged between 8 to 18 years. Dental maturity was evaluated according to the method of Demirijian et al., calcification stages of the left mandibular canines, first and second premolars and second molars were assessed. Skeletal maturity was assessed by the cervical vertebral maturation (CVM) stages according to the method of Baccetti et al. Correlation between CVM and dental maturation was evaluated by Spearman rank-order correlation coefficient (SROCC). Results: CVM and dental calcification stages were highly correlated (p<0.001) in both genders, ranging from 0.686 to 0.873 for females and 0.787 to 0.871 for males. Calcification stages of the second molars showed the strongest correlation with CVM. Conclusion: Calcification stages of the second molar may be used as a reliable maturation indicator. Dental maturation may be applied to determine the skeletal maturity status of Yemeni children and adolescents.

Objetivo: Este estudio se realizó para investigar la relación entre el desarrollo dental y las etapas de maduración vertebral cervical en un grupo de niños y adolescentes yemeníes. Material y Métodos: El estudio incluyó radiografías panorámicas digitales y cefalogramas laterales del cráneo obtenidos de 207 sujetos yemeníes: 122 mujeres y 85 hombres de entre 8 y 18 años. La madurez dental se evaluó de acuerdo con el método de Demirijian et al. Se evaluaron las etapas de calcificación de los caninos mandibulares izquierdos, primer y segundo premolares y segundos molares. La madurez esquelética se evaluó mediante las etapas de maduración vertebral cervical (CVM) de acuerdo con el método de Baccetti et al. La correlación entre la CVM y la maduración dental se evaluó mediante el coeficiente de correlación de orden de rango de Spearman (SROCC). Resultado: Las etapas de CVM y calcificación dental estuvieron altamente correlacionadas (p<0.001) en ambos sexos, con un rango de 0.686 a 0.873 para las mujeres y 0.787 a 0.871 para los hombres. Las etapas de calcificación de los segundos molares mostraron la correlación más fuerte con CVM. Conclusión: las etapas de calcificación del segundo molar pueden usarse como un indicador de maduración confiable. La maduración dental puede aplicarse para determinar el estado de madurez esquelética de los niños y adolescentes yemeníes.

Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 × 10-7). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.

Comparison between iRoot BP Plus (EndoSequence Root Repair Material) and Mineral Trioxide Aggregate as Pulp-capping Agents: A Systematic Review.

INTRODUCTION: iRoot BP Plus, also known as EndoSequence root repair material (EERM) is a premixed bioceramic thick/putty. According to its instruction manual, iRoot BP Plus is composed of tricalcium silicate, zirconium oxide, tantalum pentoxide, dicalcium silicate, calcium sulfate, calcium phosphate monobasic, and filler agents. This systematic review was carried out to evaluate and present the iRoot BP Plus material as a pulp-capping agent. MATERIALS AND METHODS: A systematic search for articles with the scope of the selection criteria undergoing for data extraction was conducted through electronic databases. Studies on evaluation of the cytotoxicity, bioactivity, and dentinal bridge formation of iRoot BP, iRoot BP Plus, ERRM putty, or ERRM paste (ERRM) on variant human cells were selected for in vitro models, and dentinal bridge formation on human and animals teeth for in vivo models were selected. RESULTS: A total of 22 articles were discussed in the review, 14 in vitro studies, five in vivo studies, and three articles with both studies. Methyl thiazol tetrazolium was the most used method for evaluating cytotoxicity. As for dentinal bridge formation, histological assessment and micro-Computed tomography were used. Human dental pulp cells (hDPCs) were the most investigated for in vitro models and rats for in vivo models. Except for one study, all studies involved in this review were primarily examining the material and comparing it to different types of mineral trioxide aggregate. CONCLUSION: iRoot BP, iRoot BP Plus, and ERRM are biocompatible materials that enhance hDPCs and other variant human cells proliferation, migration, attachment adhesion, mineralization, and dentinal bridge formation.

The Effectiveness of Micro-osteoperforations during Canine Retraction: A Three-dimensional Randomized Clinical Trial.

AIM: A major challenge in orthodontics is decreasing treatment time without compromising treatment outcome. The purpose of this split-mouth trial was to evaluate micro-osteoperforations (MOPs) in accelerating orthodontic tooth movement. MATERIALS AND METHODS: Eight patients of both genders were selected, age ranging between 15 and 40 years, with Class II Division 1 malocclusion. The participants in this trial with MOPs were randomly allocated to either the right or the left side, distal to the maxillary canine. First maxillary premolars were extracted as part of the treatment plan on both sides and then canine retraction was applied. Miniscrews were used to support anchorage. MOP side received (three small perforations) placed on the buccal bone, distal to the maxillary canine, on randomly selected side using an automated mini-implant driver and the other side was the control side. Blinding was used at the data collection and analysis stages. The primary outcome was the rate of canine retraction measured with a three-dimensional (3D) digital model from the baseline to the first 2 weeks superimposed at the rugae area from the baseline to the first, second, and third months. The following secondary outcomes were examined: anchorage loss, canine tipping, canine rotation, root resorption, plaque index, and gingival index. Pain level, pain interference with the patients' daily life, patients' satisfaction with the procedure and degree of ease, willingness to repeat the procedure, and recommendation to others were also evaluated. RESULTS: No statistically significant difference was observed in the rates of tooth movement between the MOP and the control sides at all-time points (first month: P = 0.77; mean difference, 0.2 mm; 95% CI, -0.13, 0.18 mm; second month: P = 0.50; mean difference, -0.08 mm; 95% CI, -0.33, 0.16 mm; third month: P = 0.76; mean difference, -0.05 mm; 95% CI, -0.40, 0.29 mm). There were also no differences in anchorage loss, rotation, tipping, root resorption, plaque index, periodontal index, and pain perception between the MOP and control sides at any time point (P > 0.05). MOPs had no effect on the patients' daily life except for a feeling of swelling on the first day (P = 0.05). Level of satisfaction and degree of easiness of the procedure were high. CONCLUSION: According to our clinical trial, MOPs cannot help in speeding up a canine retraction.

Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample.

BACKGROUND: Nonsyndromic cleft palate only (nsCPO) is a common and multifactorial form of orofacial clefting. In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with/without cleft palate (nsCL/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci. METHODS: We genotyped 33 SNPs at 27 candidate loci from 2 previously published nsCPO GWAS in an independent multiethnic sample. It included: (i) a family-based sample of European ancestry (n = 212); and (ii) two case/control samples of Central European (n = 94/339) and Arabian ancestry (n = 38/231), respectively. A separate association analysis was performed for each genotyped dataset, and meta-analyses were performed. RESULTS: After association analysis and meta-analyses, none of the 33 SNPs showed genome-wide significance. Two variants showed nominally significant association in the imputed GWAS dataset and exhibited a further decrease in p-value in a European and an overall meta-analysis including imputed GWAS data, respectively (rs395572: PMetaEU = 3.16 × 10-4 ; rs6809420: PMetaAll = 2.80 × 10-4 ). CONCLUSION: Our findings suggest that there is a limited contribution of common variants to nsCPO. However, the individual effect sizes might be too small for detection of further associations in the present sample sizes. Rare variants may play a more substantial role in nsCPO than in nsCL/P, for which GWAS of smaller sample sizes have identified genome-wide significant loci. Whole-exome/genome sequencing studies of nsCPO are now warranted.

Imputation of orofacial clefting data identifies novel risk loci and sheds light on the genetic background of cleft lip ± cleft palate and cleft palate only.

Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is among the most common human birth defects with multifactorial etiology. Here, we present results from a genome-wide imputation study of nsCL/P in which, after adding replication cohort data, four novel risk loci for nsCL/P are identified (at chromosomal regions 2p21, 14q22, 15q24 and 19p13). On a systematic level, we show that the association signals within this high-density dataset are enriched in functionally-relevant genomic regions that are active in both human neural crest cells (hNCC) and mouse embryonic craniofacial tissue. This enrichment is also detectable in hNCC regions primed for later activity. Using GCTA analyses, we suggest that 30% of the estimated variance in risk for nsCL/P in the European population can be attributed to common variants, with 25.5% contributed to by the 24 risk loci known to date. For each of these, we identify credible SNPs using a Bayesian refinement approach, with two loci harbouring only one probable causal variant. Finally, we demonstrate that there is no polygenic component of nsCL/P detectable that is shared with nonsyndromic cleft palate only (nsCPO). Our data suggest that, while common variants are strongly contributing to risk for nsCL/P, they do not seem to be involved in nsCPO which might be more often caused by rare deleterious variants. Our study generates novel insights into both nsCL/P and nsCPO etiology and provides a systematic framework for research into craniofacial development and malformation.

Prevalence of prematurely lost primary teeth in 5-10-year-old children in Thamar city, Yemen: A cross-sectional study.

OBJECTIVES: The premature loss of primary teeth is a potential risk factor for poor arch length development. Adequate arch length is important to the progression of the permanent teeth. Poor arch length can lead to crowding, ectopic eruption, or impaction of these teeth. This study is designed to assess the prevalence of premature loss of primary teeth in the 5-10-year-old age group. MATERIALS AND METHODS: The study group included 185 children, that is, 91 boys and 94 girls. The dental examination was conducted by an experienced examiner under sufficient artificial light. Data including patient age and missing teeth were collected. Descriptive statistics were applied for data analysis, and from the results, Chi-square tests were used at a level of significance of 5% (P < 0.05). RESULTS: We observed a 40.54% prevalence of premature loss of primary teeth with no statistically significant difference between genders. The lower left primary second molar was the most commonly absent tooth in the dental arch (13.5%). CONCLUSION: The status of premature loss of primary teeth was high in the study group. Implementation of efficient educational and preventive programs to promote oral health would help children maintain a healthy primary dentition and eventually prevent the disturbances in the future development of normal occlusion. Early detection and management of the space problems associated with the early loss of primary teeth would help in reducing malocclusion problems.

Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene.

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.

Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate.

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10(-2)). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10(-5); ORallelic = 2.46 [95% CI 1.6-3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10(-9)). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO.

Nonsyndromic cleft lip with or without cleft palate in arab populations: genetic analysis of 15 risk loci in a novel case-control sample recruited in Yemen.

BACKGROUND: Nonsyndromic orofacial clefting (nsOFC) is among the most common of all congenital disorders and has a genetically complex etiology. Based on embryological and epidemiological data, the phenotype can be differentiated into nonsyndromic cleft lip with or without cleft palate (nsCL/P) and nonsyndromic cleft palate only, with nsCL/P being the most frequent form. Recent genetic research, predominantly performed in populations from Europe and Asia, has identified numerous genetic susceptibility loci for nsCL/P. As only few data are available concerning genetic susceptibility to nsCL/P in Arab populations, we investigated a newly recruited nsOFC sample from Yemen. METHODS: For each of the 15 currently known nsCL/P risk loci, the top single-nucleotide polymorphism (plus nine back-up variants) were genotyped in 242 nsCL/P cases and 420 healthy controls. RESULTS: Single-marker association analysis revealed significant associations for four loci (8q24, 9q22, 10q25, 13q31). The strongest association was for the European high risk locus at 8q24 (Pcorrected = 5.09 × 10(-4) ; heterozygous odds ratio = 1.74 (1.22-2.47), homozygous odds ratio = 2.47 (1.55-3.93). Five additional loci (1q32.2, 3q12, 8q21, 17q22, 20q12) showed nominal significance that did not withstand correction for multiple testing. Although the six remaining loci (1p22, 1p36, 2p21, 3p11, 15q22, 17p13) failed to reach nominal significance, the risk alleles were in the same direction as in the discovery studies. CONCLUSION: The results suggest that four of the 15 analyzed nsCL/P risk loci which were identified in European and Asian ethnicities significantly confer risk for nsCL/P in Arab populations.