Effect of Orthognathic Surgery On Pulp Blood Flow and Pulp Sensibility: A Prospective Control Trial.

INTRODUCTION: Orthognathic surgery has the potential to compromise the vitality of the teeth. This paper aims to assess changes in pulp blood flow (PBF) and pulp sensibility (PS) of the anterior dentition following orthognathic surgery and to assess the influence of the proximity of the surgical osteotomy on the PBF and/or PS. METHODS: Twenty-six patients undergoing orthognathic surgery (Le Fort I or bilateral sagittal split osteotomy [BSSO]) were compared to sixteen control patients treated by fixed appliances only using Laser Doppler flowmeter (LDF) and thermal testing (CO2 snow). Surgery patients were tested at T1 (presurgery), T2 (4-5 weeks postsurgery), T3 (3 months postsurgery), and T4 (6 months postsurgery). Control patients were tested at T1 (pretreatment), T2 (6 months posttreatment), T3 (12 months posttreatment), and T4 (18 months posttreatment). Differences between the maxilla and mandible were assessed. RESULTS: No differences in PBF or PS were recorded in the control group. In the surgery group, both jaws followed the same pattern after surgery, an initial decrease at T2 followed by a gradual recovery to pretreatment PBF levels with no significant difference between T1 versus T4 in both jaws. No difference in PBF was observed between the maxilla and mandible at any testing time interval. CONCLUSIONS AND CLINICAL IMPLICATIONS: PBF and PS of the anterior dentition was severely affected immediately postsurgery, followed by a gradual increase to full recovery. This pattern of recovery was exhibited in both jaws. A negative sensibility response or discoloration should not be seen as an indication of irreversible ischemic pulp changes. Monitoring for at least 6 months or using LDF as a confirmatory test is required before any irreversible endodontic treatment is to be considered.

Optimizing the use of panoramic radiography for determining the position of impacted permanent maxillary canines.

The purpose of this research was to test the reliability of a modified magnification method for determining the position of an impacted canine from a single panoramic radiograph. This retrospective study evaluated 114 panoramic radiographs showing 136 impacted maxillary canines. The widths of the impacted canines, contralateral erupted canines, and ipsilateral maxillary incisors were measured, and ratios for the canine-incisor index (CII) and canine-canine index (CCI) were calculated. The impacted canines were also classified according to their location in the vertical plane (apical, middle, or coronal zone) relative to the contralateral central incisor. Continuous data were analyzed for normal distribution, and logistic and multivariate logistic regression models were conducted. The Benjamini-Hochberg procedure with a false discovery rate of 0.05 was used to account for multiple testing. The intrarater reliability was excellent for impacted canine, central incisor, and contralateral canine measurements (intraclass correlation coefficient > 0.9). The CII and vertical zone were strong predictors of an impacted canine position with clinically useful sensitivity and specificity values (0.69 and 0.74, respectively, based on an area under the curve concordance statistic of 0.75). A predictive range was evident for the CII of palatally (1.10-1.39) and buccally (0.90-1.19) impacted canines in the middle and coronal zones, respectively. The occurrence of palatal or buccal positioning was not significantly associated with the CCI (P = 0.2). The CII and vertical zone identified from a single panoramic radiograph can be used to determine the buccopalatal position of an impacted canine, with more reliability if the impacted canine crown is in the middle or coronal zone of the contralateral central incisor.

An evaluation of gingival phenotype and thickness as determined by indirect and direct methods.

OBJECTIVES: To evaluate gingival phenotype (GP) and thickness (GT) using visual, probing, and ultrasound (US) methods and to assess the accuracy and consistency of clinicians to visually identify GP. MATERIALS AND METHODS: The GP and GT of maxillary and mandibular anterior teeth in 29 orthodontic patients (mean age 25 ± 7.5 years) were assessed using probing and US by a single examiner. General dentist and dental specialist assessors (n = 104) were shown intraoral photographs of the patients, including six repeated images, and asked to identify the GP via a questionnaire. RESULTS: An increasing trend in GT values of thin, medium, and thick biotype probe categories was found, though this was not statistically significant (P = .188). Comparison of probing method to determinations of GT made by US yielded slight agreement (κ = 0.12). Using the visual method, assessors' identification of the second GP determination ranged from poor to moderate agreement (κ = 0.29 to κ = 0.53). CONCLUSIONS: The probe method is sufficient in differentiating between different categories of GP. However, further research is required to assess the sensitivity of the probe method in recognizing phenotypes in the most marginal of cases. Assessors using the visual method lack the ability to identify GP accurately and consistently among themselves.

Candidate genes for obstructive sleep apnea in non-syndromic children with craniofacial dysmorphisms - a narrative review.

Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) - craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia - have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population.

Effect of craniofacial morphology on gingival parameters of mandibular incisors.

OBJECTIVES: To investigate the association between the width of keratinized gingiva (WKG), gingival phenotype (GP), and gingival thickness (GT) with craniofacial morphology in sagittal and vertical dimensions. MATERIALS AND METHODS: WKG, GP, and GT of mandibular anterior teeth in 177 preorthodontic patients (mean age 18.38 ± 5.16 years) were assessed clinically using a periodontal probe, a Colorvue Biotype Probe, and ultrasound by a single examiner. Patients were grouped into skeletal Class I, II, and III and hyperdivergent, normodivergent, and hypodivergent based on ANB and SN-MP angles. Mandibular incisor inclination (L1-NB) was also measured. Clinical and cephalometric measurements were repeated to assess inter- and intraexaminer reproducibility. RESULTS: A significant association was found between thin GP and skeletal Classes I and III for the left mandibular central incisor (MCI; P = .0183). In skeletal Class III patients, L1-NB angle demonstrated a decreasing trend as phenotype thickness decreased. A significant association was found between thin phenotype and normodivergent and hypodivergent groups for MCIs (left: P = .0009, right: P = .00253). No significant association between WKG or GT and craniofacial morphology was found. CONCLUSIONS: Thin GP is associated with skeletal Class I and III for the left MCI. Thin GP is associated with hypodivergent and normodivergent skeletal patterns for the MCIs. There was no association between WKG and GT and craniofacial morphology in both skeletal and vertical dimensions. Dental compensations that exist due to different craniofacial morphology may influence the GP.

Accuracy of mandibular repositioning surgery using new technology: Computer-aided design and manufacturing customized surgical cutting guides and fixation plates.

INTRODUCTION: Recent 3-dimensional technology advancements have resulted in new techniques to improve the accuracy of intraoperative transfer. This study aimed to validate the accuracy of computer-aided design and manufacturing (CAD-CAM) customized surgical cutting guides and fixation plates on mandibular repositioning surgery performed in isolation or combined with simultaneous maxillary repositioning surgery. METHODS: Sixty patients who underwent mandibular advancement surgery by the same surgeon were retrospectively evaluated by 3-dimensional surface-based superimposition. A 3-point coordinate system (x, y, z) was used to identify the linear and angular discrepancies between the planned movements and actual outcomes. Wilcoxon rank sum test was used to compare the outcomes between the mandible-only and the bimaxillary surgery groups with significance at P <0.05. Pearson correlation coefficient compared planned mandible advancement to the outcome from advancement planned. The centroid, which represents the mandible as a single unit, was computed from 3 landmarks, and the discrepancies were evaluated by the root mean square error (RMSE) for clinical significance set at 2 mm for linear discrepancies and 4° for angular discrepancies. RESULTS: There was no statistically significant difference between the planned and actual position of the mandible in either group when considering absolute values of the differences. When considering raw directional data, a statistically significant difference was identified in the y-axis suggesting a tendency for under-advancement of the mandible in the bimaxillary group. The largest translational RMSE for the centroid was 0.77 mm in the sagittal dimension for the bimaxillary surgery group. The largest rotational RMSE for the centroid was 1.25° in the transverse dimension for the bimaxillary surgery group. Our results show that the precision and clinical feasibility of CAD-CAM customized surgical cutting guides and fixation plates on mandibular repositioning surgery is well within clinically acceptable parameters. CONCLUSION: Mandibular repositioning surgery can be performed predictably and accurately with the aid of CAD-CAM customized surgical cutting guides and fixation plates with or without maxillary surgery.

Analysis of pretreatment factors associated with stability in early class III treatment.

BACKGROUND: The purpose of this study was to identify pretreatment factors associated with the stability of early class III treatment, since most orthodontists start the treatment with their uncertain hypotheses and/or predictions. Subjects consisted of 75 patients with a class III skeletal relationship (ANB < 2° and overjet < 0 mm) who had been consecutively treated with rapid maxillary expansion and facemask and followed until their second phase treatment. The patients were divided into two groups according to whether they showed relapse in follow-up. The stable group maintained their positive overjet (n = 55), and the unstable group experienced relapse with a zero or negative overjet (n = 20). Two general, three dental, and 13 cephalometric pretreatment factors were investigated to determine which factors were associated with stability. RESULTS: Sex, pretreatment age, and anteroposterior functional shift, which were hypothesized as associated factors, were not related to the stability of early class III treatment. Significant differences were detected between the two groups in the horizontal distance between the maxillary and mandibular molars in centric relation. Cephalometric variables, such as the mandibular length (Ar-Me), Wits appraisal, SN to ramus plane angle (SN-Rm), gonial angle, incisor mandibular plane angle (IMPA), and Frankfort plane to mandibular incisor angle (FMIA) showed significant differences between the groups. The horizontal distance was the most influential factor by logistic regression analysis. CONCLUSIONS: Hypothesis (related to sex, age, functional shift) were rejected. Several cephalometric factors related to the mandible were associated with stability. The horizontal distance between the maxillary and mandibular molars in centric relation was the best predictor of early class III treatment relapse.

Heredity, Genetics and Orthodontics - How Much Has This Research Really Helped?

Uncovering the genetic factors that correlate with a clinical deviation of previously unknown etiology helps to diminish the unknown variation influencing the phenotype. Clinical studies, particularly those that consider the effects of an appliance or treatment regimen on growth, need to be a part of these types of genetic investigations in the future. While the day-to-day utilization of "testing" for genetic factors is not ready for practice yet, genetic testing for monogenic traits such as Primary Failure of Eruption (PFE) and Class III malocclusion is showing more promise as knowledge and technology advances. Although the heterogeneous complexity of such things as facial and dental development, the physiology of tooth movement, and the occurrence of External Apical Root Resorption (EARR) make their precise prediction untenable, investigations into the genetic factors that influence different phenotypes, and how these factors may relate to or impact environmental factors (including orthodontic treatment) are becoming better understood. The most important "genetic test" the practitioner can do today is to gather the patient's individual and family history. This would greatly benefit the patient, and augment the usefulness of these families in future clinical research in which clinical findings, environmental, and genetic factors can be studied.

Aging, inflammation, immunity and periodontal disease.

The increased prevalence and severity of periodontal disease have long been associated with aging, such that this oral condition affects the majority of the adult population over 50 years of age. Although the immune system is a critical component for maintaining health, aging can be characterized by quantitative and qualitative modifications of the immune system. This process, termed 'immunosenescence', is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasia and autoimmunity, presumably reflecting the prolonged antigenic stimulation and/or stress responses that occur across the lifespan. Interestingly, the global reduction in the host capability to respond effectively to these challenges is coupled with a progressive increase in the general proinflammatory status, termed 'inflammaging'. Consistent with the definition of immunosenescence, it has been suggested that the cumulative effect of prolonged exposure of the periodontium to microbial challenge is, at least in part, a contributor to the effects of aging on these tissues. Thus, it has also been hypothesized that alterations in the function of resident immune and nonimmune cells of the periodontium contribute to the expression of inflammaging in periodontal disease. Although the majority of aging research has focused on the adaptive immune response, it is becoming increasingly clear that the innate immune compartment is also highly affected by aging. Thus, the phenomenon of immunosenescence and inflammaging, expressed as age-associated changes within the periodontium, needs to be more fully understood in this era of precision and personalized medicine and dentistry.

Comparison of BMI, AHI, and apolipoprotein E ε4 (APOE-ε4) alleles among sleep apnea patients with different skeletal classifications.

STUDY OBJECTIVES: This case-control study investigated whether variations within the APOE-ε gene were associated with having a convex facial profile (skeletal Class II) compared to exhibiting a straight or concave facial profile (Class I or Class III) among patients with obstructive sleep apnea (OSA). Associations between the apnea-hypopnea index (AHI) and body mass index (BMI) scores for these OSA patients were also examined in the context of facial profile. METHOD: OSA patients with an AHI ≥ 15 were recruited from a sleep clinic and classified by facial and dental occlusal relationships based on a profile facial analysis, lateral photographs, and dental examination. Saliva was collected as a source of DNA. The APOE-ε1-4 allele-defining single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped. A χ(2) analysis was used to assess Hardy-Weinberg equilibrium and for association analysis (significance at p < 0.05). ANOVA and Fisher exact test were also used. RESULT: Seventy-six Caucasian OSA patients participated in the study-25 Class II cases and 51 non-Class II cases. There was no association of the APOE-ε4 allele with facial profile among these OSA patients. Class II OSA patients had significantly lower BMIs (30.7 ± 5.78) than Class I (37.3 ± 6.14) or Class III (37.8 ± 6.17) patients (p < 0.001), although there was no statistical difference in AHI for Class II patients compared with other groups. CONCLUSION: OSA patients with Class II convex profile were more likely to have a lower BMI than those in other skeletal groups. In fact 20% of them were not obese, suggesting that a Class II convex profile may influence or be associated with OSA development independent of BMI.

Genetics and non-syndromic facial growth.

Just as pediatricians and endocrinologists are interested in understanding statural growth patterns and the prediction of adult height, pediatric dentists, orthodontists, and oral/maxillofacial surgeons need to be knowledgeable about a patient's facial growth patterns to effectively treat them. Some variations in facial growth have been clinically associated with a poor esthetic self-image, malocclusion formation and the development of physical and/or functional deformity. To understand how different genetic factors influence growth and development patterns, scientists and clinicians study developmental sequences, malformations and syndromes. While understanding this general information can be clinically valuable when making treatment decisions for an individual and their family, the greatest contribution of genetics in clinical practice may be in the form of personalized or "precision" medicine in the general population. Precision medicine takes into account knowing a portion or all of a patient's specific DNA code to estimate how their genetic makeup will influence growth and development patterns. Ultimately, the identification of key genetic variations at the level of the individual patient can improve growth predictions for that patient and may be indicative of how well they will respond to specific forms of treatment.

Total IgA and IgA reactivity to antigen I/II epitopes in HLA-DRB1*04 positive subjects.

Bacterial adherence to the acquired dental pellicle, important in dental caries (caries), is mediated by receptor-adhesins such as salivary agglutinin binding to Streptococcus mutans antigen I/II (I/II). Ten selected I/II epitopes were chosen to determine their reactivity to human salivary IgA. Previous studies suggested that a specific HLA biomarker group (HLA-DRB1*04) may have differential influence of immune responses to I/II. However, it was not known whether secretory IgA (SIgA) responses to the selected epitopes from HLA-DRB1*04 positive subjects were different compared to controls, or across other caries-related factors such as total IgA (TIgA). Thirty-two total subjects were matched according to HLA type, gender, ethnicity and age. HLA genotyping, oral bacterial, immunoglobulin and antibody analyses were performed. A large observed difference emerged with regard to the natural immune reservoir of TIgA in HLA-DRB1*04 positive subjects, specifically, a 27.6% reduction compared to controls. In contrast to all other epitopes studied, HLA-DRB1*04 positive subjects also exhibited reduced reactivity to I/II epitope 834-853. HLA-DRB1*04 positive subjects exhibited lower specific SIgA activity/TIgA to 834-853 and also a lower specific reactivity to 834-853/whole cell S. mutans UA159. Furthermore, HLA-DRB1*04 positive subjects exhibited lower responses to I/II in its entirety. The large observed difference in TIgA and the 834-853 reactivity pattern across multiple measures suggest potentially important connections pertaining to the link between HLA-DRB1*04 and caries.

Association between CYP19A1 genotype and pubertal sagittal jaw growth.

INTRODUCTION: Sagittal jaw growth is influenced during puberty by a ratio of androgens and estrogens. The CYP19A1 (formerly CYP19) gene encodes the cytochrome P450 enzyme aromatase (estrogen synthetase), which converts testosterone to estrogen. Genetic variations including single nucleotide polymorphisms might regulate CYP19A1 gene expression or the function of the aromatase protein and thus influence sagittal jaw growth. METHODS: The annual sagittal jaw growth in 92 pubertal orthodontic patients was determined by using pretreatment and posttreatment cephalometric radiographs. Single nucleotide polymorphisms rs2470144 and rs2445761 were genotyped and haplotypes constructed. Associations between genotypes or haplotypes and the annual sagittal growth were estimated by using JMP (version 9.0; SAS Institute, Cary, NC). RESULTS: Two single nucleotide polymorphisms were significantly associated with average differences in annual sagittal jaw growth in boys. Haplotype analysis demonstrated that haplotypes T(rs2470144)T(rs2445761) and C(rs2470144)T(rs2445761) had significant effects on annual sagittal maxillary growth and on mandibular growth in boys. No association was found in girls. CONCLUSIONS: A quantitative trait locus that influences male pubertal sagittal jaw growth might exist in the CYP19A1 gene, and single nucleotide polymorphisms rs2470144 and rs2445761 might be inside this quantitative trait locus or be linked to it.

Evaluation of retention protocols among members of the American Association of Orthodontists in the United States.

INTRODUCTION: Little research has been conducted to evaluate protocols and trends in orthodontic retention. The purpose of this study was to identify the general retention protocols used by orthodontists in the United States. Additionally, our goal was to identify trends in these orthodontic retention protocols by evaluating how they have changed over the past 5 years and how they might continue to change in the next 5 years. METHODS: The study was conducted via a 36-question electronic survey (REDCap, Nashville, Tenn) with branching logic on certain questions. The survey was sent to all 9143 practicing members of the American Association of Orthodontists in the United States, and 1632 (18%) responded. RESULTS AND CONCLUSIONS: Mean retention protocols of the surveyed population showed predominant use of Hawley or vacuum-formed retainers in the maxillary arch and fixed retention in the mandibular arch. For both arches, there is a current shift away from Hawley retainers and toward vacuum-formed retainers and fixed retention. Respondents who extract fewer teeth reported increased use of fixed retention in the maxillary (P = 0.041) and mandibular (P = 0.003) arches. Respondents who extract fewer teeth and use removable retainers were more likely to tell their patients to wear their retainers at night for the rest of their lives (P = 1.63 × 10(-6)).

Dental maturity of Caucasian children in the Indianapolis area.

PURPOSE: The purpose of this study was to compare chronologic and dental age using Demirjian's method. METHODS: Two hundred and fifty-seven panoramic radiographs of healthy 5- to 17.5-year-old Caucasian children in the Indianapolis area were evaluated using Demirjian's 7 tooth method. RESULTS: The intraclass correlation coefficient (ICC) for agreement with Demirjian was 0.94 (95% confidence interval [CI]: 0.87, 0.97). The ICC for repeatability of the investigator was 0.97 (95% CI=0.95, 0.99). Calculated dental age was significantly greater than chronologic age by 0.59 years (P<.001). There was no significant difference in the mean difference in ages between sexes (P=.73). Medicaid subjects had a significantly higher (P<.001) mean difference (0.82 years) than private insurance subjects (0.32 years). There was a significant negative correlation between the chronologic age and the difference in ages (r=-0.29, P<.001). Overweight (P<.001) and obese (P=.004) subjects were significantly more dentally advanced than normal (P=.35) and underweight (P=.42) subjects. CONCLUSIONS: Demirjian's method has high inter- and intraexaminer repeatability. Caucasian children in the Indianapolis area are more advanced dentally than the French-Canadian children studied by Demirjian. Difference between dental age and chronologic age varies depending on the age of the child, socioeconomic status, and body mass index.

Clinical outcomes for patients finished with the SureSmile™ method compared with conventional fixed orthodontic therapy.

OBJECTIVE: Utilize American Board of Orthodontics (ABO) cast/radiographic evaluation (CRE) to compare a series of 63 consecutive patients, finished with manual wire bending (conventional) treatment, vs a subsequent series of 69 consecutive patients, finished by the same orthodontist using the SureSmile™ (SS) method. MATERIALS AND METHODS: Records of 132 nonextraction patients were scored by a calibrated examiner blinded to treatment mode. Age and discrepancy index (DI) between groups were compared by t-tests. A chi-square test was used to compare for differences in sex and whether the patient was treated using braces only (no orthopedic correction). Analysis of covariance tested for differences in CRE outcomes and treatment times, with sex and DI included as covariates. A logarithmic transformation of CRE outcomes and treatment times was used because their distributions were skewed. Significance was defined as P < .05. RESULTS: Compared with conventional finishing, SS patients had significantly lower DI scores, less treatment time (∼7 months), and better CRE scores for first-order alignment-rotation and interproximal space closure; however, second-order root angulation (RA) was inferior. CONCLUSION: SS patients were treated in less time to better CRE scores for first-order rotation (AR) and interproximal space closure (IC) but on the average, malocclusions were less complex and second order root alignment was inferior, compared with patients finished with manual wire bending.

Orthodontic mechanotransduction and the role of the P2X7 receptor.

INTRODUCTION: The P2X7 receptor plays a crucial role in bone biology and inflammation. Its main function is to promote necrotic tissue metabolism by ensuring a normal acute-phase inflammatory response. We used a mouse model to describe and compare orthodontic mechanotransduction in wild-type and P2X7 knock-out mice. METHODS: By using finite element analysis, mouse orthodontic mechanics were scaled to produce typical human stress levels. External root resorption, bone modeling, and bone remodeling were analyzed with fluorescent bone labels, Masson trichrome stain, and microcomputed tomography. Relationships between the biologic responses and the calculated stresses were statistically tested and compared between mouse types. RESULTS: There were direct relationships between certain stress magnitudes and root resorption and bone formation. Hyalinization and root and bone resorption were different in the 2 types of mice. CONCLUSIONS: Orthodontic responses are related to the principal stress patterns in the periodontal ligament, and the P2X7 receptor plays a significant role in their mechanotransduction.

Comparison of the Bolton Standards to longitudinal cephalograms superimposed on the occipital condyle (I-point).

OBJECTIVE: To compare traditional superimposition on sella turcica and the anterior cranial base (SACB) to superimposition referenced at the occipital condyle (I-point) for demonstrating craniofacial growth and development. MATERIALS AND METHODS: Tracings for ages 8, 10, 12, 15 and 18 were chosen from the Bolton Standards of Dentofacial Developmental Growth to compare superimposition with the traditional longitudinal reference at SACB (anterior curvature of sella turcica and anterior cranial base) to reference at I-point on the antero-inferior contour of the occipital condyles in norma lateralis. The serial tracings were superimposed using both the sagittal and postero-anterior (PA) tracings. Incremental growth of landmarks was measured in relation to Cartesian coordinates and compared between the superimposition methods. RESULTS: Sagittal and PA tracing superimpositions displayed an average 7 mm greater cephalad movement of landmarks, an average 2.4 mm greater ventral movement, and comparable transverse dimension with superimposition referenced at I-point as compared to the SACB reference. CONCLUSION: I-point superimposition demonstrates physiologic growth patterns concealed by traditional registration at sella turcica. The evolution of superimposition on SACB was based on convenience and reproducibility. Fundamental principles of bone development are consistent with the occipital condyles as a more biologic reference for relative craniofacial growth. Actual vertical growth is believed to be greater than displayed in this study, due to the cross-sectional and blended nature of the sample.

Inheritance of susceptibility to root resorption associated with orthodontic force in mice.

INTRODUCTION: External apical root resorption (EARR) is an unwanted sequelae of orthodontic treatment. Genetic factors account for approximately 64% of the EARR variation in humans. Inbred mice offer a model to control the environmental factors and genetic heterogeneity that complicate human genetic studies. Genetically distinct inbred mice and their offspring (F1s) were analyzed to examine the mode of inheritance and the influence of parental sex on the susceptibility to root resorption associated with orthodontic force (RRAOF). METHODS: RRAOF was determined histologically for male and female mice of the A/J, DBA/2J, and BALB/cJ strains, and the A/JxDBA/2J and A/JxBALB/cJ crosses (10 males and 10 females/reciprocal cross). RRAOF was induced by tipping the maxillary first molar mesially for 9 days. RESULTS: Sex differences were observed only among the mice of the BALB/cJ strain. Two patterns of inheritance were observed; F1s from the A/JxBALB/cJ cross were resistant, suggesting that the A/J have dominant resistance alleles. On the other hand, F1s from the A/JxDBA/2J cross showed RRAOF intermediate between their parental mice, suggesting a polygenic trait. CONCLUSIONS: These results provide evidence of a traceable and polygenetic component affecting RRAOF in mice.

A comprehensive analysis of normal variation and disease-causing mutations in the human DSPP gene.

Within nine dentin dysplasia (DD) (type II) and dentinogenesis imperfecta (type II and III) patient/families, seven have 1 of 4 net -1 deletions within the approximately 2-kb coding repeat domain of the DSPP gene while the remaining two patients have splice-site mutations. All frameshift mutations are predicted to change the highly soluble DSPP protein into proteins with long hydrophobic amino acid repeats that could interfere with processing of normal DSPP and/or other secreted matrix proteins. We propose that all previously reported missense, nonsense, and splice-site DSPP mutations (all associated with exons 2 and 3) result in dominant phenotypes due to disruption of signal peptide-processing and/or related biochemical events that also result in interference with protein processing. This would bring the currently known dominant forms of the human disease phenotype in agreement with the normal phenotype of the heterozygous null Dspp (-/+) mice. A study of 188 normal human chromosomes revealed a hypervariable DSPP repeat domain with extraordinary rates of change including 20 slip-replication indel events and 37 predominantly C-to-T transition SNPs. The most frequent transition in the primordial 9-basepair (bp) DNA repeat was a sense-strand CpG site while a CpNpG (CAG) transition was the second most frequent SNP. Bisulfite-sequencing of genomic DNA showed that the DSPP repeat can be methylated at both motifs. This suggests that, like plants and some animals, humans methylate some CpNpG sequences. Analysis of 37 haplotypes of the highly variable DSPP gene from geographically diverse people suggests it may be a useful autosomal marker in human migration studies.