Early loss of primary teeth among children in Thamar city, Yemen

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

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 and Methods: The study included digital panoramic radiographs and lateral skull cephalograms obtained from 207 Yemeni subjects—122 females and 85 males aged between 8 to 18 years. Dental maturity was evaluated according to the method of Demirijian et al.,6 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.10 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&lt;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.6 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.10 La correlación entre la CVM y la maduración dental se evaluó mediante el coeficiente de correlación de orden de rango de Spearman (SROCC). Resultados: Las etapas de CVM y calcificación dental estuvieron altamente correlacionadas (p&lt;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

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

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.Funding information: The present study was supported by the German Research Foundation (DFG)-Grants BE 3828/8-1, LU 1944/2-1, MA 2546/5-1, and LU1944/3-1. ACKNOWLEDGMENTS: The authors thank all patients, relatives, and control individuals for their participation. We thank the German support group for individuals with cleft lip and/or palate (Wolfgang Rosenthal Gesellschaft) for assistance with recruitment.We acknowledge the invaluable assistance of all clinical, laboratory, and bioinformatic personnel. The authors thank the Next Generation Sequencing Core Facility of the Medical Faculty of the University of Bonn for sequencing the samples that were used in this study. DbGaP datasets were accessed through dbGaP accession number phs000094.v1.p1 (Supplemental Acknowledgments). Finally, the authors thank the Genome Aggregation Database (gnomAD), and all groups that provided exome and genome variant data to this resource. A full list of gnomAD contributors is provided in the gnomAD flagship paper (Karczewski et al., 2020). Open Access funding enabled and organized by Projekt DEAL

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.

Abstract 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 signalswithin this high-density datasetare 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 refinementapproach, 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

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

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.Clefts of the lip and palate are common birth defects, and require long-term multidisciplinary management. Their etiology involves genetic factors and environmental influences and/or a combination of both, however, these interactions are poorly defined. Moreover, although clefts of the lip may or may not involve the palate, the determinants predisposing to specific subphenotypes are largely unknown. Here we demonstrate that variations in the non-coding region near the GREM1 gene show a highly significant association with a particular phenotype in which cleft lip and cleft palate co-occ

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.The present study was supported by the German Research Foundation (DFG)-Grants BE 3828/8-1, LU 1944/2-1, MA 2546/5-1, and LU1944/3-1

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

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&rsquo;s alpha values extended from 0.90 to 0.92 (intra-class correlations = 0.85&ndash;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&ndash;0.98; p &lt; 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 &lt; 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