Heritability of dental arches and occlusal characteristics: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The genetic basis of dentoalveolar characteristics has been investigated by several studies, however, the findings are equivocal. The objective of this systematic review and meta-analysis was to evaluate the heritability of dental arches and occlusal parameters in different stages of human dentition. SEARCH METHODS: Electronic databases PubMed, Embase, Scopus, Web of Science, and Dentistry and Oral Science Source were searched up to August 2023 without the restriction of language or publication date. SELECTION CRITERIA: Empirical studies investigating the heritability of dentoalveolar parameters among twins and siblings were included in the review. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, and risk of bias assessment were performed independently and in duplicate by two authors and a third author resolved conflicts if needed. Joanna Briggs Institute's critical appraisal tool was used to evaluate the risk of bias among studies and the certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Twenty-eight studies were included in the systematic review, of which 15 studies reporting heritability coefficients in the permanent dentition stages were deemed suitable for the meta-analysis. Random-effects meta-analyses showed high heritability estimates for maxillary intermolar width (0.52), maxillary intercanine width (0.54), mandibular intermolar width (0.55), mandibular intercanine width (0.55), maxillary arch length (0.76), mandibular arch length (0.57), and palatal depth (0.56). The heritability estimates for the occlusal parameters varied considerably, with relatively moderate values for crossbite (0.46) and overbite (0.44) and low values for buccal segment relationship (0.32), overjet (0.22), and rotation and displacement of teeth (0.16). However, the certainty of evidence for most of the outcomes was low according to the GRADE criteria. CONCLUSIONS: Based on the available evidence, it can be concluded that the dental arch dimensions have a high heritability while the occlusal parameters demonstrate a moderate to low heritability. REGISTRATION: PROSPERO (CRD42022358442).

Patterns of heritability across the human diphyodont dental complex: Crown morphology of Australian twins and families.

OBJECTIVES: This study generates a series of narrow-sense heritability estimates for crown morphology of the deciduous and permanent dentition with two overarching aims. The first is to test the hypothesis that deciduous teeth provide a more faithful reflection of genetic information than their permanent successors. The second is to use quantitative genetic methods to evaluate assumptions underlying common data collection and analysis practices in biodistance research. MATERIALS AND METHODS: Dental morphology data were collected from longitudinal dental casts representing Australian twins and families using Arizona State Dental Anthropology System standards. Polygenic models and estimates of narrow-sense heritability were generated using SOLAR v.8.1.1. Each model considered age, sex, and age/sex interaction as covariates. RESULTS: Heritability estimates significantly differed from zero for the majority of morphological crown characters. Most estimates fell within the 0.4-0.8 range typically observed for crown morphology. Mean heritability was stable across the dental complex, but for paired homologues, permanent traits often yielded higher estimates than their deciduous counterparts. Results indicate directional asymmetry in environmental influence for crown morphology and inform biodistance "best practices" related to data collection and treatment. CONCLUSIONS: Overall, results for this sample support the use of crown morphology as a proxy for genetic variation in evolutionary research. This includes the deciduous dentition, which justifies the expansion of efforts to incorporate subadults into reconstructions of past microevolutionary processes. Results do not indicate that deciduous phenotypes more closely approximate underlying genotype, at least for deciduous/permanent homologues.

Three-dimensional (3D) geometric morphometric analysis of human premolars to assess sexual dimorphism and biological ancestry in Australian populations.

OBJECTIVES: This study aimed to investigate size and shape variation of human premolars between Indigenous Australians and Australians of European ancestry, and to assess whether sex and ancestry could be differentiated between these groups using 3D geometric morphometrics. MATERIALS AND METHODS: Seventy dental casts from each group, equally subdivided by sex, were scanned using a structured-light scanner. The 3D meshes of upper and lower premolars were processed using geometric morphometric methods. Seventy-two landmarks were recorded for upper premolars and 50 landmarks for lower premolars. For each tooth type, two-way ANOVA was used to assess group differences in centroid size. Shape variations were explored using principal component analysis and visualized using 3D morphing. Two-way Procrustes ANOVA was applied to test group differences for ancestry and sex, and a "leave-one-out" discriminant function was applied to assess group assignment. RESULTS: Centroid size and shape did not display significant difference between the sexes. Centroid size was larger in Indigenous Australians for upper premolars and lower second premolars compared to the Australians of European ancestry. Significant shape variation was noted between the two ancestral groups for upper premolars and the lower first premolar. Correct group assignment of individual teeth to their ancestral groups ranged between 80.0 and 92.8% for upper premolars and 60.0 and 75.7% for lower premolars. DISCUSSION: Our findings provide evidence of significant size and shape variation in human premolars between the two ancestral groups. High classification rates based on shape analysis of upper premolars highlight potential application of geometric morphometrics in anthropological, bioarcheological and forensic contexts.

Mirror, mirror? An evaluation of identical twin mirroring in tooth crown morphology.

It has been estimated that 25% of monozygotic ("identical") twin pairs exhibit reverse asymmetry (RA) or "mirroring" of minor anatomical features as a result of delayed zygote division. Here, we examine whether identical twin mirroring accounts for patterns of dental asymmetry in a sample of monozygotic and dizygotic ("fraternal") twins. We focus on crown morphology to approach the following question: is there an association between dental RA frequency and twin type suggestive of the presence of mirror image twins in our sample? Data were collected from 208 deciduous and 196 permanent dentitions of participants of the University of Adelaide Twin Study using Arizona State University Dental Anthropology System standards. RA frequencies were compared across morphological complexes (deciduous, permanent), twin types (monozygotic, dizygotic), and traits. Fisher's exact tests were performed to formally evaluate the association between twin type and dental RA. Across the entire dataset, RA rates failed to exceed 8% for any twin type. In monozygotic twins, deciduous mirroring totaled 5.3% of observed cases, while permanent mirroring totaled 7.8% of observed cases. We found no statistically significant association between RA and twin type for any morphological character (p-value range: 0.07-1.00). Our results suggest the timing of monozygotic twin division does not explain the structure of asymmetry for our morphology dataset and that published estimates of identical twin mirroring rates may be inflated or contingent upon phenotype. Instead, rates reported for this sample more closely align with the proposed etiology of this condition.

Late Complications in Long-Term Childhood Cancer Survivors: What the Oral Health Professional Needs to Know.

With diagnostic and therapeutic advances, over 80% of children diagnosed with cancer become long-term survivors. As the number of childhood cancer survivors (CCS) continues to increase, dental practitioners become more likely to have CCS among their patients. CCS may develop late complications from damage caused by their cancer treatment to endocrine, cardiovascular, musculoskeletal, and other organ systems. These complications may surface decades after the completion of treatment. Adverse outcomes of childhood cancer treatment frequently involve oral and craniofacial structures including the dentition. Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function may be disturbed, increasing oral health risks in these individuals. Moreover, CCS are at risk of developing subsequent malignancies, which may manifest in or near the oral cavity. It is important that dental practitioners are aware of the childhood cancer history of their patients and have knowledge of potential late complications. Therefore, this narrative review aims to inform dental practitioners of late oral complications of cancer treatment modalities commonly used in pediatric oncology. Furthermore, selected common non-oral late sequelae of cancer therapy that could have an impact on oral health and on delivering dental care will be discussed.

Genetic, epigenetic, and environmental influences on dentofacial structures and oral health: ongoing studies of Australian twins and their families.

The Craniofacial Biology Research Group in the School of Dentistry at The University of Adelaide is entering an exciting new phase of its studies of dental development and oral health in twins and their families. Studies of the teeth and faces of Australian twins have been continuing for nearly 30 years, with three major cohorts of twins recruited over that time, and currently we are working with twins aged 2 years old to adults. Cross-sectional data and records relating to teeth and faces of twins are available for around 300 pairs of teenage twins, as well as longitudinal data for 300 pairs of twins examined at three different stages of development, once with primary teeth, once at the mixed dentition stage, and then again when the permanent teeth had emerged. The third cohort of twins comprises over 600 pairs of twins recruited at around birth, together with other family members. The emphasis in this third group of twins has been to record the timing of emergence of the primary teeth and also to sample saliva and dental plaque to establish the timing of colonization of decay-forming bacteria in the mouth. Analyses have confirmed that genetic factors strongly influence variation in timing of primary tooth emergence. The research team is now beginning to carry out clinical examinations of the twins to see whether those who become colonized earlier with decay-forming bacteria develop dental decay at an earlier age. By making comparisons within and between monozygotic (MZ) and dizygotic (DZ) twin pairs and applying modern molecular approaches, we are now teasing out how genetic, epigenetic, and environmental factors interact to influence dental development and also oral health.

Genetic and Morphological Variation in Hypodontia of Maxillary Lateral Incisors.

(1) Background: Hypodontia has a multifactorial aetiology, in which genetic factors are a major component. Associated with this congenital absence, the formed teeth may show differences in size and shape, which may vary with the specific genetic variants and with the location of the missing teeth. The aims of the present study were to investigate a specific variant of MSX1, derive morphometric tooth measurements in a sample of patients with isolated maxillary lateral incisor agenesis and matched controls, and model the findings. (2) Methods: Genotyping of the MSX1 rs8670 genetic variant and morphometric measurements with a 2D image analysis method were performed for 26 hypodontia patients and 26 matched controls. (3) Results: The risk of upper lateral incisor agenesis was 6.9 times higher when the T allele was present. The morphometric parameters showed significant differences between hypodontia patients and controls and between the unilateral and bilateral agenesis cases. The most affected crown dimension in the hypodontia patients was the bucco-lingual dimension. In crown shape there was significant variation the Carabelli trait in upper first molars. (4) Conclusions: The MSX1 rs8670 variant was associated with variations in morphological outcomes. The new findings for compensatory interactions between the maxillary incisors indicate that epigenetic and environmental factors interact with this genetic variant. A single-level directional complex interactive network model incorporates the variations seen in this study.

The Oral Health of a Group of 19th Century South Australian Settlers in Relation to Their General Health and Compared with That of Contemporaneous Samples.

The aims of this study are to determine the oral health status of a rare sample of 19th-century migrant settlers to South Australia, how oral conditions may have influenced their general health, and how the oral health of this group compares with contemporaneous samples in Australia, New Zealand, and Britain. Dentitions of 18 adults and 22 subadults were investigated using non-destructive methods (micro-CT, macroscopic, radiographic). Extensive carious lesions were identified in seventeen adults and four subadults, and from this group one subadult and sixteen adults had antemortem tooth loss. Sixteen adults showed evidence of periodontal disease. Enamel hypoplastic (EH) defects were identified in fourteen adults and nine subadults. Many individuals with dental defects also had skeletal signs of comorbidities. South Australian individuals had the same percentage of carious lesions as the British sample (53%), more than other historic Australian samples, but less than a contemporary New Zealand sample. Over 50% of individuals from all the historic cemeteries had EH defects, suggesting systemic health insults during dental development were common during the 19th century. The overall oral health of the South Australian settlers was poor but, in some categories, (tooth wear, periapical abscess, periodontal disease), better than the other historic samples.

Association of GSTTI, M1 and Polymorphism in GSTPI with Chronic Periodontal Disease in a Pakistani Population.

OBJECTIVE: Chronic periodontal disease (CP) is a multifactorial infectious and inflammatory disease that occurs due to the challenge between the immune response of the host and specific periodontal bacteria, and that can lead to tooth loss due to damage inflicted to the supporting tissue. The current study investigates the genotypes of the GSTM1 and GSTT1 genes, along with the allelic frequency of the single nucleotide polymorphism [SNP; rs1695] in the GSTP1 gene and correlates them individually or in various combinations with the incidence of CP. METHODS: A total of 203 clinically confirmed CP patients and 201 control subjects were enrolled from Multan and Dera Ghazi Khan Districts in Pakistan from April to July 2022. Multiplex Polymerase Chain Reaction (PCR) and tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) approaches were applied to determine the genotypes of the studied GSTs. The association of rs1695 in GSTP1 with CP was studied both individually and in various combinations with GSTM1 and T1. RESULTS: The absence of GSTM1, the presence of GSTT1 and the presence of the mutant allele (G) at rs1695 in GSTP1 were found to be significantly associated with CP. Patients aged between 10 and 30 years were more affected by CP. CONCLUSION: Our results indicate that the genotypes of the analyzed GSTs affect the levels of protection from oxidative stress and may therefore influence the disease progression in CP.

Phenotype-genotype correlations in mouse models of amelogenesis imperfecta caused by Amelx and Enam mutations.

Mutations in human and in mouse orthologous genes Amelx and Enam result in a diverse range of enamel defects. In this study we aimed to investigate the phenotype-genotype correlation between the mutants and the wild-type controls in mouse models of amelogenesis imperfecta using novel measurement approaches. Ten hemi-mandibles and incisors were dissected from each group of Amelx(WT), Amelx(X/Y64H), Amelx(Y/Y64H), Amelx(Y64H/Y64H), and Enam(WT), Enam(Rgsc395) heterozygous and Enam(Rgsc395) homozygous mice. Their macro-morphology, colour and micro-topography were assessed using bespoke 2D and 3D image analysis systems and customized colour and whiteness algorithms. The novel methods identified significant differences (p ≤ 0.05) between the Amelx groups for mandible and incisor size and enamel colour and between the Enam groups for incisor size and enamel colour. The Amelx(WT) mice had the largest mandibles and incisors, followed in descending order of size by the Amelx(X/Y64H), Amelx(Y/Y64H) and Amelx(Y64H/Y64H) mice. Within the Enam groups the Enam(WT) incisors were largest and the Enam(Rgsc395) heterozygous mice were smallest. The effect on tooth morphology was also reflected by the severity of the enamel defects in the colour and whiteness assessment. Amelogenin affected mandible morphology and incisor enamel formation, while enamelin only affected incisors, supporting the multifunctional role of amelogenin. The enamelin mutation was associated with earlier forming enamel defects. The study supported the critical involvement of amelogenin and enamelin in enamel mineralization.

Genetic, environmental and epigenetic influences on variation in human tooth number, size and shape.

The aim of this review is to highlight some key recent developments in studies of tooth number, size and shape that are providing better insights into the roles of genetic, environmental and epigenetic factors in the process of dental development. Advances in molecular genetics are helping to clarify how epigenetic factors influence the spatial and temporal regulation of the complex processes involved in odontogenesis. At the phenotypic level, the development of sophisticated systems for image analysis is enabling new dental phenotypes to be defined. The 2D and 3D data that are generated by these imaging systems can then be analysed with mathematical approaches, such as geometric morphometric analysis. By gathering phenotypic data and DNA from twins, it is now possible to use 'genome-wide' association studies and the monozygotic co-twin design to identify important genes in odontogenesis and also to clarify how epigenetic and environmental factors can affect this process. Given that many of the common dental anomalies affecting the human dentition are interrelated, apparently reflecting pleiotropic genetic effects, the discoveries and new directions described in this paper should have important implications for clinical dental practice in the future.

Evaluating the effectiveness of countywide mask mandates at reducing SARS-CoV-2 infection in the United States.

CONTEXT: With the rise of the Delta variant of SARS-CoV-2 and the low vaccination rates in the United States, mitigation strategies to reduce the spread of SARS-CoV-2 are essential for protecting the health of the general public and reducing strain on healthcare facilities. This study compares US counties with and without mask mandates and determines if the mandates are associated with reduced daily COVID-19 infection. US counties have debated whether masks effectively decrease COVID-19 cases, and political pressures have prevented some counties from passing mask mandates. This article investigates the utility of mask mandates in small US counties. OBJECTIVES: This study aims to analyze the effectiveness of mask mandates in small US counties and places where the population density may not be as high as in larger urban counties and to determine the efficacy of countywide mask mandates in reducing daily COVID-19 infection. METHODS: The counties studied were those with populations between 40,000 and 105,000 in states that did not have statewide mask mandates. A total of 38 counties were utilized in the study, half with and half without mask mandates. Test counties were followed for 30 days after implementing their mask mandate, and daily new SARS-CoV-2 infection was recorded during this timeframe. The counties were in four randomly selected states that did not have statewide mask mandates. The controls utilized were from counties with similar populations to the test counties and were within the same state as the test county. Controls were followed for the same 30 days as their respective test county. Data were analyzed utilizing t-test and difference-in-difference analyses comparing counties with mask mandates and those without. RESULTS: These data showed statistically significant lower averages of SARS-CoV-2 daily infection in counties that passed mask mandates when compared with counties that did not. The difference-in-difference analysis revealed a 16.9% reduction in predicted COVID-19 cases at the end of 30 days. CONCLUSIONS: These data support the effectiveness of mask mandates in reducing SARS-CoV-2 infection spread in small US counties where the population density may be less than in urban counties. Small US counties that are considering passing mask mandates for the population can utilize these data to justify their policy considerations.

Genetic, Epigenetic and Environmental Factors Influence the Phenotype of Tooth Number, Size and Shape: Anterior Maxillary Supernumeraries and the Morphology of Mandibular Incisors.

The aim of this study is to investigate whether the genetic, epigenetic and environmental factors that give rise to supernumeraries in the maxillary incisor region and larger dimensions of the adjacent maxillary incisors are also associated with variations in the morphology of the mandibular incisors. If so, this would contribute to understanding the distribution and interactions of factors during dental development and how these can be modelled. The sample consisted of 34 patients with supernumerary teeth in the maxillary anterior region, matched for gender, age and White Caucasian ethnicity with 34 control subjects. The average ages of the supernumerary and control groups were 12.8 and 12.2 years, respectively. Study models of all subjects were constructed and imaged using a previously validated system. Using custom software, each of the mandibular incisor teeth were measured to obtain 17 parameters from the labial view and 17 from the occlusal view. Principal component analysis (PCA) was used to summarize the measurements into a smaller set representing distinct features of the clinical crowns, followed by a comparison between the supernumerary and control groups using 2-way ANOVA. Seven factors of tooth size of the mandibular central incisors and six factors of the mandibular lateral incisors were identified as major features of the clinical crowns. All parameters of both mandibular incisors were greater in the supernumerary group than in the control, with three of these, located in the incisal and cervical regions of the mandibular lateral incisors, being statistically significantly larger. The findings of this study indicate that the aetiological factors associated with supernumerary teeth in the maxillary anterior region also affect tooth crown dimensions of mandibular incisors. This new evidence enhances several models of the interactions of genetic, epigenetic and environmental components of dental development and supports a multi-model approach to increase understanding of this process and its variations.

Genetic Correlation, Pleiotropy, and Molar Morphology in a Longitudinal Sample of Australian Twins and Families.

This study aims to expand our understanding of the genetic architecture of crown morphology in the human diphyodont dentition. Here, we present bivariate genetic correlation estimates for deciduous and permanent molar traits and evaluate the patterns of pleiotropy within (e.g., m1-m2) and between (e.g., m2-M1) dentitions. Morphology was observed and scored from dental models representing participants of an Australian twin and family study (deciduous n = 290, permanent n = 339). Data collection followed Arizona State University Dental Anthropology System standards. Genetic correlation estimates were generated using maximum likelihood variance components analysis in SOLAR v.8.1.1. Approximately 23% of deciduous variance components models and 30% of permanent variance components models yielded significant genetic correlation estimates. By comparison, over half (56%) of deciduous-permanent homologues (e.g., m2 hypocone-M1 hypocone) were significantly genetically correlated. It is generally assumed that the deciduous and permanent molars represent members of a meristic molar field emerging from the primary dental lamina. However, stronger genetic integration among m2-M1/M2 homologues than among paired deciduous traits suggests the m2 represents the anterior-most member of a "true" molar field. The results indicate genetic factors act at distinct points throughout development to generate homologous molar form, starting with the m2, which is later replaced by a permanent premolariform crown.

Was it worth migrating to the new British industrial colony of South Australia? Evidence from skeletal pathologies and historic records of a sample of 19th-century settlers.

OBJECTIVES: To examine pathological evidence present in a sample of 19th -century settlers to South Australia in the context of an early industrial society. MATERIALS: Skeletal remains of 20 adults and 45 nonadults from the government funded burial site (free ground) of St Mary's Anglican Church Cemetery, gravestones of privately funded burials and local parish records. METHODS: Investigation of pathological manifestations of skeletal remains, church records and historic literature. Comparison with similar samples from Britain and from New South Wales. RESULTS: Joint disease seen in 35% of adults. Porosity in bone cortices indicative of vitamin C deficiency seen in 32% of the total sample and porous lesions in the orbit (cribra orbitalia) in 7% of nonadults. Traumatic fractures identified in two adult males. Gastrointestinal conditions were the leading cause of death for nonadults, most adults died of pulmonary conditions. Life expectancy of people buried at the expense of the government was 23.8-42.6 years, those in private burials 57.1 years. CONCLUSION: Health of migrant settlers from the St Mary's free ground did not differ much from that of a similar population in Britain nor of settlers in New South Wales. Thus, it is characteristic for lower socioeconomic groups in early industrialised societies. SIGNIFICANCE: St Mary's sample is a rarity due scarcity of similar Australian skeletal samples. LIMITATIONS: Small sample size and lack of similar samples for comparison. SUGGESTIONS FOR FURTHER RESEARCH: Comprehensive investigation of dentitions in St Mary's sample and studies of more skeletal samples of early settlers in other Australian locations.

Health effects of European colonization: An investigation of skeletal remains from 19th to early 20th century migrant settlers in South Australia.

The British colony of South Australia, established in 1836, offered a fresh start to migrants hoping for a better life. A cohort of settlers buried in a section of St Mary's Anglican Church Cemetery (1847-1927) allocated for government funded burials was investigated to determine their health, with a focus on skeletal manifestations associated with metabolic deficiencies. Findings of St Mary's sample were compared with those published for contemporary skeletal samples from two British cemeteries, St Martin's, Birmingham, and St Peter's, Wolverhampton, to explore similarities and differences. To investigate the changing economic background of the St Mary's cohort, which may have influenced the location of their burial within the cemetery, the number and demographic profile of government funded burials and those in privately funded leased plots were compared. The study sample consisted of the skeletal remains of 65 individuals (20 adults, 45 subadults) from St Mary's Cemetery 'free ground' section. The bones and teeth of individuals in this cohort showed evidence of pathological manifestations, including areas of abnormal porosity in bone cortices in 9 adults and 12 subadults and flaring of metaphyses (one subadult) and costochondral junctions of the ribs (one subadult). Porous lesions of orbital roof bones (Types 3 to 4) were seen on three subadults. Macroscopic examination of teeth identified enamel hypoplastic defects and micro-CT scans showed areas of interglobular dentine. Comparison of St Mary's findings with the British samples revealed that prevalences of manifestations associated with vitamin C deficiency were higher at St Mary's and manifestations associated with vitamin D deficiency were lower respectively. The location of burial pattern at St Mary's Cemetery, from the mid-1840s to1860s, showed differences in the economic status of migrants. This pattern changed from the 1870s, which reflected improvements in the local economy and the economic recovery of the colony.

Tooth Formation as Experimental Model to Study Chemotherapy on Tissue Development: Effect of a Specific Dose of Temozolomide/Veliparib.

BACKGROUND: Chemotherapy treatment of cancer in children can influence formation of normal tissues, leading to irreversible changes in their structure and function. Tooth formation is susceptible to several types of chemotherapy that induce irreversible changes in the structure of enamel, dentin and dental root morphology. These changes can make the teeth more prone to fracture or to caries when they have erupted. Recent studies report successful treatment of brain tumors with the alkylating drug temozolomide (TMZ) in combination with veliparib (VLP) in a glioblastoma in vivo mouse model. Whether these drugs also affect tooth formation is unknown. AIM: In this study the effect of TMZ/VLP on incisor formation was investigated in tissue sections of jaws from mice and compared with mice not treated with these drugs. MATERIALS AND METHOD: The following aspects were studied using immunohistochemistry of specific protein markers including: (1) proliferation (by protein expression of proliferation marker Ki67) (2) a protein involved in paracellular ion transport (expression of tight junction (TJ) protein claudin-1) and (3) in transcellular passage of ions across the dental epithelium (expression of Na+, K+ 2Cl- cotransporter/NKCC1). RESULTS: Chemotherapy with TMZ/VLP strongly reduced immunostaining for claudin-1 in distal parts of maturation ameloblasts. No gross changes were found in the treated mice, either in cell proliferation in the dental epithelium at the cervical loop or in the immunostaining pattern for NKCC1 in (non-ameloblastic) dental epithelium. The salivary glands in the treated mice contained strongly reduced immunostaining for NKCC1 in the basolateral membranes of acinar cells. DISCUSSION/CONCLUSIONS: Based on the reduction of claudin-1 immunostaining in ameloblasts, TMZ/VLP may potentially influence forming enamel by changes in the structure of TJs structures in maturation ameloblasts, structures that are crucial for the selective passage of ions through the intercellular space between neighboring ameloblasts. The strongly reduced basolateral NKCC1 staining seen in fully-grown salivary glands of TMZ/VLP-treated mice suggests that TMZ/VLF could also influence ion transport in adult saliva by the salivary gland epithelium. This may cause treated children to be more susceptible to caries.

The genetic architecture of anterior tooth morphology in a longitudinal sample of Australian twins and families.

OBJECTIVE: This study presents a quantitative genetic analysis of human anterior dental morphology in a longitudinal sample of known genealogy. The primary aim of this work is to generate a suite of genetic correlations within and between deciduous and permanent characters to access patterns of integration across the diphyodont dental complex. DESIGN: Data were recorded from casted tooth crowns representing participants of a long-term Australian twin and family study (deciduous n = 290, permanent n = 339). Morphological trait expression was observed and scored following Arizona State University Dental Anthropology System standards. Bivariate genetic correlations were estimated using maximum likelihood variance decomposition models in SOLAR v.8.1.1. RESULTS: Genetic correlation estimates indicate high levels of integration between antimeres but low to moderate levels among traits within a tooth row. Only 9% of deciduous model comparisons were significant, while pleiotropy was indicated for one third of permanent trait pairs. Canine characters stood out as strongly integrated, especially in the deciduous dentition. For homologous characters across dentitions (e.g., deciduous i1 shoveling and permanent I1 shoveling), ∼70% of model comparisons yielded significant genetic correlations. CONCLUSIONS: Patterns of genetic correlation suggest a morphological canine module that spans the primary and secondary dentition. Results also point to the existence of a genetic mechanism conserving morphology across the diphyodont dental complex, such that paired deciduous and permanent traits are more strongly integrated than characters within individual tooth rows/teeth.

A large X-chromosomal deletion is associated with microphthalmia with linear skin defects (MLS) and amelogenesis imperfecta (XAI).

A female patient is described with clinical symptoms of both microphthalmia with linear skin defects (MLS or MIDAS) and dental enamel defects, having an appearance compatible with X-linked amelogenesis imperfecta (XAI). Genomic DNA was purified from the patient's blood and semiquantitative multiplex PCR revealed a deletion encompassing the amelogenin gene (AMELX). Because MLS is also localized to Xp22, genomic DNA was subjected to array comparative genomic hybridization, and a large heterozygous deletion was identified. Histopathology of one primary and one permanent molar tooth showed abnormalities in the dental enamel layer, and a third tooth had unusually high microhardness measurements, possibly due to its ultrastructural anomalies as seen by scanning electron microscopy. This is the first report of a patient with both of these rare conditions, and the first description of the phenotype resulting from a deletion encompassing the entire AMELX gene. More than 50 additional genes were monosomic in this patient.