Orodental malformations associated with human MSX1 sequence variants.

BACKGROUND: MSX1 sequence variants have been known to cause human tooth agenesis (TA) with or without orofacial clefts. However, their roles during the whole processes of tooth development are not fully understood. This study aimed to characterize a 4-membered family with TA carrying a novel MSX1 pathogenic variant and investigate the disease mechanism. METHODS: The authors conducted whole exome analysis to define the disease-causing sequence variant. They performed microcomputed tomography, morphometric analyses, transcriptome profiling, and molecular characterization to study the affected teeth and the gene variant. RESULTS: The authors identified an MSX1 pathogenic variant, p.Glu232∗, in affected family members with TA and concomitant orodental anomalies, namely, prominent maxillary labial frenum, central incisor diastema, median maxillary anterior alveolar cleft, tooth fusion, mandibular molar dysmorphology, thin dentin layer, and slender dental roots. MSX1-defective teeth were not apparently microdontic but had thin dentin layers. The mandibular molars showed a homeotic transformation to maxillary counterparts. Genes involved in extracellular matrix organization and dentinogenesis, such as DMP1 and MMP20, were downregulated in dental pulp tissues of MSX1-defective teeth. The p.Glu232∗-truncated MSX1 properly localized to the nucleus but partially lost its transactivation ability. Analyzing reported cases indicated that truncation sequence variants within the homeobox domain of MSX1 caused a more severe TA phenotype than those outside of the homeobox domain, probably due to dominant negativity compared with haploinsufficiency. CONCLUSIONS: This study provides in vivo evidence that MSX1 contributes to developmental processes of various orodental tissues in humans. PRACTICAL IMPLICATIONS: Clinically, hypertrophic labial frenum, incisor diastema, and median maxillary anterior alveolar cleft might be considered diagnostic for MSX1-associated TA.

The implication of instructional design for deciduous tooth identification in a dental morphology course for undergraduate dental students.

Background/purpose: The pediatric dentistry courses are lacking in our six-year undergraduate dental education. The purpose of this study was to evaluate the implication of instructional design for deciduous tooth identification in a dental morphology course for undergraduate dental students through students' perspectives. Materials and methods: A total of 34 s-year dental students who took this dental morphology course were invited to fill out the questionnaire for survey of instructional design for deciduous tooth identification after the class. Results: Of the 34 dental students, 32 of them participated in the survey with a valid response rate of 94.1%. The results showed that most students found the learning activity of instructional design for deciduous tooth identification to be helpful for improving their knowledge about deciduous dentition. Most of them also had positive attitude towards this instructional design. Conclusion: Since the proportion of pediatric dentistry courses in the undergraduate dental education is very low and children's oral problems are indeed faced by all dentists, it is important to add learning units of pediatric dentistry-related knowledge in different undergraduate dental professional courses or to propose strategies to promote students' awareness of self-directed learning about pediatric dentistry. This study may serve as a model for other undergraduate dental courses in Taiwan.

Sleep and its association with dental caries or myopia in first graders.

AIM: First grade is a transition from pre-school to school-age. The change in lifestyle behaviours such as sleep may have a physiological response, which contributes to the presence or absence of two highly incident diseases: dental caries or myopia. The aim of the study was to examine the association between sleep and myopia as well as sleep and dental caries in first graders. DESIGN: It is a cross-sectional study. METHODS: This was a recruitment phase of an interventional study. A total of 338 children whose caregivers completed a Children's Sleep Habits Questionnaire. Caregivers also provided information regarding myopia and caries status of children and their parents. Binary logistic regression was applied to analyse the potential risk factors. RESULTS: Dental caries and myopia rates were 45.9% and 9.5%, respectively. After adjusting for children's gender, children's age, fathers with caries and mothers with caries, the odds ratio for dental caries in children who slept less than 9 h when compared to those who slept for nine and more hours was 1.94. Mothers with caries were 3.37 times more likely to have children with caries than mothers without caries. However, sleep was not associated with myopia in first graders. CONCLUSION: Sleeping less than 9 h and maternal caries were risk factors of children developing dental caries. Future sleep and myopia studies can be conducted on higher graders who may present prolonged exposure and accumulations of myopic risk factors. IMPLICATIONS: Screening of children with insufficient sleep is needed for nurses to enable the early identification of high-risk groups for dental caries in school settings. Family nurses are encouraged to work with family members to implement tailored sleep interventions, in order to facilitate better sleep and oral health practices in both school and home settings. REGISTRATION: This study protocol was registered on ClinicalTrials.gov (Registration number: Redacted).

The implication of integrating pediatric education into a pediatric dentistry course for undergraduate dental students.

Background/purpose: The separation of dentistry and medicine was initiated as a historical root. The purpose of this study was to evaluate the implication of integrating pediatric education into a pediatric dentistry course (so-called the integrated pediatric dentistry course in this study) for undergraduate dental students through students' perspectives. Materials and methods: A total of the 34 fifth-year dental students were invited to fill out the questionnaire for the integrated pediatric dentistry course survey after the class of integrated pediatric dentistry course. Results: Of the 34 dental students, all participated in the survey with a 100% valid response rate. The results showed that most of dental students found this integrated pediatric dentistry course to be helpful in improving their knowledge and clinical skills for pediatric dentistry, and knowledge about pediatrics related to dentistry. However, in comparison, the acquisition of clinical skills was less than that of knowledge for pediatric dentistry. Conclusion: We conclude that the integrated pediatric dentistry course improves dental students' knowledge and clinical skills about pediatric dentistry, and knowledge about pediatrics related to dentistry. Considering the effectiveness of this integrated pediatric dentistry course on students' knowledge and clinical skills, and positive attitude towards pediatric dentistry, this model shows promising for the further use in the dental education.

Correlation between dental professionally topical fluoride application and children's dental use for dental caries under the National Health Insurance system in Taiwan from 2008 to 2021.

Background/purpose: Dental caries is one of the most common oral diseases in children worldwide, especially in Taiwan. This study investigated dental professionally topical fluoride application (PTFA) and children's dental use for dental caries under the National Health Insurance (NHI) system in Taiwan from 2008 to 2021. Materials and methods: The population data and medical records of the NHI system were obtained from the websites of the Ministry of the Interior and the Ministry of Health and Welfare, respectively. The dental PTFA services and dental use indicators for dental caries were analyzed from 2008 to 2021. Results: The number of out-patient visits for dental PTFA services increased from 221,675 in 2008 to 1,078,099 in 2021. The total increase of the out-patient visits was 856,424 with a total increase rate of 386.34%. The one-year increase was 65,879 with a one-year increase rate of 29.72%. Among the 3 age groups of children, their dental use indicators almost presented decreasing trends from 2008 to 2021. Moreover, in general, the dental use indicators showed a negative correlation with the number of the overall out-patient visits for dental PTFA services from 2008 to 2021. Conclusion: In Taiwan, there is a negative correlation between the dental use indicators in NHI system and the number of the overall out-patient visits for dental PTFA services from 2008 to 2021. However, the problem of dental caries in children is still serious and there is still a space for improvement in the oral health education for child caregivers and children.

The dental use for periodontal diseases under the national health insurance system in Taiwan in 2021.

Background/purpose: Periodontal disease is one of the main oral diseases in humans. This study investigated the dental use for periodontal diseases under the National Health Insurance system (NHI) system in Taiwan in 2021. Materials and methods: The population data and medical records of the NHI system were obtained from the websites of the Ministry of the Interior and the NHI Administration, respectively. The dental patient data were divided into 18 age groups to analyze the dental use indicators for periodontal diseases under the NHI system in Taiwan in 2021. Results: The dental use rate for treatment of periodontal diseases (including gingivitis and periodontitis) had the highest peak (51.85%) in the 5-9-year age group under the NHI system in Taiwan in 2021. It dropped abruptly to a lower point (38.20%) in the 15-19-year age group, fluctuated and declined gradually with increasing age, and finally dropped to the lowest point of 18.78% in the greater than 85-year age group. Furthermore, the number of out-patient visits per 1000 people showed a similar trend. However, the medical expenses per person also showed a similar trend except the findings of the highest peak in the 55-59-year age groups. Conclusion: Periodontal disease is still the main disease of the oral cavity in Taiwan. From a cost-effectiveness viewpoint, Taiwan government shall develop a better oral health policy to decrease the incidence of periodontal diseases and to prevent periodontal diseases from deteriorating into the end age of tooth loss for all citizens, especially for patients of special needs.

FAM20A mutations and transcriptome analyses of dental pulp tissues of enamel renal syndrome.

AIM: Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications. METHODOLOGY: Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control. RESULTS: Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues. CONCLUSIONS: Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.

PAX9 mutations and genetic synergism in familial tooth agenesis.

Familial tooth agenesis (FTA) is one of the most common craniofacial anomalies in humans. Loss-of-function mutations in PAX9 and WNT10A have been known to cause FTA with various expressivity. In this study, we identified five FTA kindreds with novel PAX9 disease-causing mutations: p.(Glu7Lys), p.(Val83Leu), p.(Pro118Ser), p.(Ser197Argfs*23), and c.771+4A>G. Concomitant PAX9 and WNT10A pathogenic variants found in two probands with severe phenotypes suggested an effect of mutational synergism. All overexpressed PAX9s showed proper nuclear localization, excepting the p.(Pro118Ser) mutant. Various missense mutations caused differential loss of PAX9 transcriptional ability. PAX9 overexpression in dental pulp cells upregulated LEF1 and AXIN2 expression, indicating a positive regulatory role for PAX9 in canonical Wnt signaling. Analyzing 176 cases with 63 different mutations, we observed a distinct pattern of tooth agenesis for PAX9-associated FTA: Maxillary teeth are in general more frequently affected than mandibular ones. Along with all second molars, maxillary bicuspids and first molars are mostly involved, while maxillary lateral incisors and mandibular bicuspids are relatively less affected. Genotypically, missense mutations are associated with fewer missing teeth than frameshift and nonsense variants. This study significantly expands the phenotypic and genotypic spectrums of PAX9-associated disorders and reveals a molecular mechanism of genetic synergism underlying FTA variable expressivity.

Overview of dental professionally topical fluoride application in public health measure in Taiwan in 2021.

Background/purpose: In Taiwan, it has been 16 years since the policy of children's dental professionally topical fluoride application (PTFA) services was implemented. This study investigated the differences in the number of children's dental PTFA outpatient visits among cities and counties or different regions of Taiwan in 2021. Materials and methods: The population data and medical records of the number of children's dental PTFA outpatient visits were obtained from the websites of Ministry of the Interior and Ministry of Health and Welfare, respectively. The secondary data were divided by cities and counties to analyze the urban-rural gap and regional differences in the number of children's dental PTFA outpatient visits in Taiwan in 2021. Results: In Taiwan, municipalities had the largest number of dental PTFA visits (721,338, 66.91% of the total dental PTFA visits), while remote and outlying island counties had the smallest number of dental PTFA visits (84,509, 7.84%). The northern region had the largest number of dental PTFA visits (466,728, 43.29%), while outlying islands had the smallest number of dental PTFA visits (25,055, 2.32%). Based on the children aged 3-5 years, municipalities had the lowest dental PTFA use rate (171.70%), while remote and outlying island counties had the highest dental PTFA use rate (482.96%). Conclusion: In Taiwan, there is a higher number of children's dental PTFA outpatient visits in municipalities than in non-municipalities or remote and outlying island counties as well as in northern region than in each of other four regions (central, southern, and eastern regions and outlying islands).

An exploration of the connotation of clinical dental radiology education for medical radiation students in Taiwan in 2022.

Background/purpose: In Taiwan, the dental radiology has a history of more than 100 years. However, medical radiation schools or teaching hospitals have not yet established a set of standard learning content for dental radiology internship. Materials and methods: We used the observational method and dental radiology teaching survey to explore the connotation of clinical dental radiology education for medical radiation students in Taiwan. Results: There were 64 dental departments of hospitals with their own independent dental radiology departments in Taiwan in 2022. Among them, 58 (90.63%) were in the teaching hospitals. Of the 58 dental radiology departments in the teaching hospitals, 40 (68.97%) had medical radiation interns in their dental radiology departments. There was a complete set of seven training items for dental radiology internship. The mean training items in the medical centers (4.94) was significantly higher than that in the regional hospital (3.9) (P < 0.05). No matter what level of hospital, it is the most common way to implement the training mode with preclinical exercises and then clinical practice. Conclusion: In Taiwan, the current status of dental radiology teachers in the teaching hospital is indeed seriously insufficient. It is necessary to establish a standard dental radiology education system, including setting one common dental radiology subject for medical radiation students, and the relevant regulations to formulate the basic requirements of the training items and training hours for dental radiology internship. Thus, medical radiation interns can acquire the operation skills related to dental X-ray machines after completing the internship training.

Overview of dental education system and gender distribution of undergraduate dental students in Taiwan.

Abstract Background/purpose: The gender distribution of dentists in Taiwan has been dominated by male dentists for a long time. This study analyzed preliminarily the appearance of the current dental education system and the gender distribution of undergraduate dental students. Materials and methods: This study used documentary analysis and secondary data analysis to survey mainly the current dental education system and the gender distribution of undergraduate dental students in Taiwan. Results: There were a total of 2474 dental students and 394 dental graduates in Taiwan in 2021. The numbers of male students (1435, 58.00%) and male graduates (207, 52.54%) were higher than those of female students (1039, 42.00%) and female graduates (187, 47.46%). The numbers of male dental students in the northern (629), central (428), and southern (378) regions were all higher than those of female dental students (423, 373, and 243, respectively). The chi-square test indicated the significantly higher proportion of male dental students in the northern and southern regions (P < 0.01). Besides, there were a total of 15,857 registered dentists. The number of male dentists (10,997, 69.35%) was higher than that of female dentists (4,860, 30.65%). Compared with population, the chi-square test showed the significantly higher proportion of male dental students and male registered dentists (all P-values < 0.001). Conclusion: In Taiwan, the dental education system must promote female students' interest in dentistry and elevate the proportion of female dental supervisors to increase the proportion of female dental students and female dentists in the future.