Transcriptome Sequencing of Gingival Tissues from Impacted Third Molars Patients Reveals the Alterations of Gene Expression.

OBJECTIVE: The removal of impacted third molars by surgery may occur with a series of complications, whereas limited information about the postoperative pathogenesis is available. The objective of this study is to identify changes in gene expression after flap surgical removal of impacted third molars and provide potential information to reduce postoperative complications. METHODS: The gingival tissues of twenty patients with flap surgical removal of impacted third molars and twenty healthy volunteers were collected for gene expression testing. The collected gingival tissues were used RNA sequencing technology and quantitative real-time PCR validation was performed. DEG was mapped to protein databases such as GO and KEGG for functional annotation and, based on annotation information, for mining of differential expression genes in patients with mpacted third molars. RESULTS: A total of 555 genes were differentially expressed. Among the top up-regulated genes, HLA-DRB4, CCL20, and CXCL8 were strongly associated with immune response and signal transduction. Among the top down-regulated genes, SPRR2B, CLDN17, LCE3D and LCE3E were related to keratinocyte differentiation, IFITM5, and BGLAP were related to bone mineralization, UGT2B17 is associated with susceptibility to osteoporosis. KEGG results showed that the DEGs were related to multiple disease-related pathways. CONCLUSION: This first transcriptome analysis of gingival tissues from patients with surgical removal of impacted third molars provides new insights into postoperative genetic changes. The results may establish a basis for future research on minimizing the incidence of complications after flap-treated third molars.

Non-coding RNAs transcribed from ultra-conserved regions (T-UCRs) are differentially expressed in dental follicle tissues of impacted mandibular third molars.

INTRODUCTION: Transcribed ultra-conserved regions (T-UCRs) are a new class of long non-coding RNA molecules transcribed from ultra-conserved regions (UCRs) of the human genome. T-UCRs are extremely conserved in the human, rat, and mouse genomes. Deletions of genomic areas containing UCRs resulted in live mice that developed without distinguishable phenotypes, implying that T-UCRs are involved in developmental processes. In addition, there is increasing evidence that dental follicle tissues exhibit various cellular alterations involving deregulation of protein-coding genes and non-coding RNAs. Accordingly, the main objective of the present study was to determine the clinical significance and distinct expression signatures of non-coding RNA molecules transcribed from ultra-conserved regions in dental follicle tissues of impacted mandibular third molars. MATERIALS AND METHODS: From March 2021 to December 2021, a total of 42 patients who referred to clinic of oral and maxillofacial surgery department with the indications of impacted mandibular third molar extraction from 38th and 48th positions were enrolled for the study. For the analysis of T-UCR expression levels, real-time quantitative reverse transcription PCR method was used. RESULTS: Findings of the present study indicated that T-UCRs are distinctly expressed in dental follicle tissues of impacted mandibular third molars. The expression of uc.38, uc.112, and uc.338 was found to be significantly increased in the dental follicles of impacted mandibular third molars, indicating a clinical significance of these molecules. In addition, no differences in T-UCR expression were found as a function of demographic characteristics. CONCLUSIONS: Collectively, transcribed ultra-conserved elements, such as uc.38, uc.112, and uc.338, are considerably deregulated in the dental follicle tissues of impacted mandibular third molars and might be responsible for the molecular changes acquired by dental follicle tissues of impacted mandibular third molars.

Investigation of the expression level of long non-coding RNAs in dental follicles of impacted mandibular third molars.

OBJECTIVES: Dental follicle (DF) is made up of mesenchymal cells and fibers surrounding the enamel organ of a developing tooth. It has been shown that cystic and neoplastic lesions can develop from the pericoronal follicles of impacted third molars (ITMs). But the molecular transformation of DF tissues has not yet been uncovered and remains elusive. Accordingly, in the present study, we aimed to investigate the differential expression of lncRNA genes in DF tissues associated with asymptomatic impacted mandibular third molars (IMTMs) that do not show pathological pericoronal radiolucency in radiographic examination. MATERIAL AND METHODS: A total of 30 patients with unilateral mesioangular IMTMs were enrolled for the study. The expressions of lncRNA genes were determined in the DF and healthy gingival tissues obtained from study patients. For the determination of lncRNA expression levels, RNA was isolated from the obtained tissues, converted to cDNA samples, and analyzed by quantitative real-time PCR method. RESULTS: As a result, we found that the gene expression of MEG3 was increased about 10-fold in DF tissues compared to healthy gingival tissues (p < 0.0001). In addition, NORAD expression was found to be upregulated 4.2-fold (p = 0.0002) in DF tissues. Also, expression level of MALAT1 was found to be decreased 1.24-fold (p = 0.584) and TP73-AS1 increased 2.6-fold (p = 0.093) in DF tissues compared to healthy gingival tissues. CONCLUSIONS: Consequently, present findings suggest that differentially expressed lncRNAs in DFs might be associated with the various levels of cellular events including osteogenic differentiation, DNA damage, and the transformation into odontogenic pathology. CLINICAL RELEVANCE: Expression levels of MEG3 and NORAD lncRNA molecules may guide clinicians in the evaluation of asymptomatic ITM dental follicles that cannot be determined radiologically and during extraction of these teeth for prophylactic purposes.

Genetic Pattern, Orthodontic and Surgical Management of Multiple Supplementary Impacted Teeth in a Rare, Cleidocranial Dysplasia Patient: A Case Report.

Background: Cleidocranial dysplasia (CCD) is a rare, autosomal dominant skeletal dysplasia with a prevalence of one per million births. The main causes of CCD are mutations in the core-binding factor alpha-1 (CBFA1) or runt-related transcription factor-2 (RUNX2), located at the 6p21 chromosomal region. RUNX2 plays important roles in osteoblast differentiation, chondrocyte proliferation and differentiation, and tooth formation. The disease is characterized by clavicular aplasia or hypoplasia, Wormian bones, delayed closure of cranial suture, brachycephalic head, maxillary deficiency, retention of primary teeth, inclusion of permanent teeth, and multiple supernumerary teeth. Materials and Methods: A 22-year-old girl suffering from cleidocranial dysplasia with short stature, narrow shoulders, craniofacial manifestations (short face, broad forehead, etc.) and dental anomalies (different lower dental elements under eruption, supernumerary and impacted multiple teeth, etc.) was examined at our service (Complex Operative Unit of Odontostomatology of Policlinico of Bari). RX Orthopantomography (OPG) and cone beam computed tomography (CBCT) were requested to better assess the position of the supernumerary teeth and their relationships with others and to evaluate the bone tissue. Results: Under eruption was probably caused by dental interferences with supernumerary teeth; hence, extractions of supernumerary upper canines and lower premolars were performed under general anaesthesia. Surgery outcome was excellent with good tissue healing and improvements in the therapeutic possibilities with future orthodontics. Conclusions: The objective of this article is to give an update about radiological, clinical, and molecular features of CCD and to alert the health team about the importance of establishing an early diagnosis and an appropriate treatment in these patients to prevent impacted teeth complications and to offer them a better quality of life.

Common dental features and craniofacial development of three siblings with Ter Haar syndrome.

BACKGROUND: Ter Haar syndrome is a rare genetic syndrome with <30 cases reported worldwide. There is nothing within the published literature regarding the dental development and dental features of these patients. CASE REPORT: This case series examines three patients with Ter Haar syndrome and tracks their dental development and identifies common dental and skeletal features. FOLLOW-UP: All three patients received dental treatment and regular follow-up at Great Ormond Street Hospital Dental Department. CONCLUSION: These patients have many common dental and craniofacial features which poses the question as to whether these features are due to Ter Haar syndrome.

Gardner's syndrome: a clinical and genetic study of a family.

OBJECTIVE: Gardner syndrome (GS) is an autosomal dominant genetic disorder with almost complete penetrance (80%) and variable expression. GS is a variant of familial adenomatous polyposis and characterized by extracolonic manifestations including osteomas and soft tissue tumors (desmoid tumors, epidermoid cysts). We describe clinical and surgical approaches in a family in which the genetic disorder was diagnosed in 3 generations. STUDY DESIGN: The studied family underwent clinical history and instrumental and genomic studies. Two members of this family, affected with GS, underwent surgery for skeletal osteomas. RESULTS: The patients that we treated with clinical-instrumental monitoring for a period of 5 years had no major disturbances of the stomatognathic system and no clinical signs of pathology of the gastrointestinal tract, eyes, or endocrine systems. CONCLUSIONS: The orofacial complex disorders are exclusively functional and esthetic, concerning primarily the stomatognathic system. We had no cases of malignant transformation of osteomatosis lesions. Clinical sequelae are manly facial eumorphy and occlusion problems of the temporomandibular joint.

Linkage analysis confirms heterogeneity of hereditary gingival fibromatosis.

OBJECTIVES: Hereditary Gingival Fibromatosis (HGF) is a rare benign fibrous lesion of the gingival tissues presumably caused by single gene defects. The aim of this study was to identify the genetic defect leading to HGF in an extended pedigree. MATERIALS AND METHODS: We report the clinical features and genetic analysis of a family affected by HGF. A total of 17 subjects were assessed clinically and had blood samples taken for DNA extraction. Multipoint parametric linkage analysis was performed to identify the possible chromosomal location responsible for HGF in this family. RESULTS: Presence of severe HGF associated with tooth impaction was confirmed for seven members of this three-generation family. Linkage analysis revealed that loci on chromosomes 7, 10, 13, 15, 16, 17, 19 and 20 were linked to this trait. Previously found mutations in the SOS1 and GINGF loci were therefore excluded by this analysis. CONCLUSIONS: This study brings further evidence for genetic heterogeneity of HGF and points towards the existence of different, not-yet-identified genes linked to this condition.

Differing therapeutic approaches to cleidocranial dysplasia (CCD).

Cleidocranial dysplasia (CCD) (MIM 119600) is a genetic skeletal disorder characterised by skeletal alterations at numerous bone segments (cranium, clavicles, pelvis) and a typical hyperdontia. It is a hereditary disease of the dominant autosomal type with wide variability of expression. The constant presence of numerous supernumerary teeth poses two orders of problems. On one hand, if these supplementary teeth are impacted, they may constitute a mechanical obstacle to the eruption of normal teeth. If on the contrary they have erupted, they cause aesthetic and functional damage. Surgical therapy is indispensable to restore a correct architecture to the alveolar-dental arches, and it is recommended during childhood to avoid or at least reduce complications in adulthood. Two cases of cleidocranial dysplasia are here reported. The adult patient (Case 1), reached our observation with a poor oral situation, manifested relapsing odontogenic abscesses at several impacted supernumerary teeth. The surgical treatment was complex and invasive, requiring percutaneous access in order to remove a tooth embedded in the mandible and the extraction of almost all residual teeth. This outcome was avoided in the second case, through combined surgical-orthodontic treatment that entailed extraction of the supernumerary teeth and subsequent orthodontic treatment, with restoration of a normal occlusion. In conclusion, management of patients suffering from very rare pathologies should be carefully evaluated in relation to clinical characteristics and possible local and systemic complications. The aim of this study is to illustrate two cases managed in a paradigmatically opposite way. It is paramount for the surgeon to intercept cases of hyperodontia typical of CCD at an early phase. It is possible, through correct surgical-orthodontic treatment, not only to avoid local and general complications, but also to achieve proper occlusion.

The sequential hypothesis of impaction of maxillary canine - a hypothesis based on clinical and radiographic findings.

The aetiology of impacted maxillary canines remains obscure. Numerous researchers have focused on identifying specific and non-specific aetiological factors responsible for canine displacement. Currently, the two most popular hypotheses that have gained consensus worldwide are the guidance theory and the genetic theory. However, no single hypotheses, can completely explain the aetiology of impaction of maxillary canines. This retrospective study was used to develop and postulate the aetiology of both buccally and palatally impacted maxillary canines. The study was conducted on a sample of 533 patients for whom the pattern and distribution of the impacted maxillary canines, sex differences, the dental age of the patients, dental anomalies and various geometric measurements which were made on the panoramic radiographs were recorded. Based on these findings, the sequential hypothesis of impaction of the maxillary canine was postulated. The hypothesis states that both buccally and palatally impacted canines have similar aetiological factors leading to their impaction. It is suggested that genetic mechanisms strongly influence the potential of the maxillary canine to be impacted and the guidance from the lateral incisor and the stage of development plays a vital role in determining the ultimate position of the impacted canine.

Cleidocranial dysplasia: oral features and genetic analysis of 11 patients.

BACKGROUND: Cleidocranial dysplasia (CCD) is a dominantly inherited autosomal disease characterized by typical bone defects including short stature, persistently open or delayed closure of the cranial sutures, and hypoplastic or aplastic clavicles. Oral features are frequent and include supernumerary teeth, delayed eruption or impaction of the permanent teeth, and malocclusion. Heterozygous mutations in RUNX2 gene, which encodes a transcription factor essential for osteoblast differentiation, were identified as the etiological cause of CCD. OBJECTIVE AND METHODS: Herein, we performed physical and radiographic examination and screening for RUNX2 mutations in 11 patients from five families with CCD. RESULTS: All patients demonstrated the classical phenotypes related to CCD. Families whose affected members had several dental alterations such as multiple impacted and supernumerary teeth demonstrated heterozygous missense mutations (R190Q and R225Q) that impair the runt domain of RUNX2. On the other hand, CCD patients from families with low frequency of dental abnormalities showed no mutation in RUNX2 or mutation outside of the runt domain (Q292fs→X299). CONCLUSION: The current findings suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes in CCD and to identify other factors that might influence the clinical features of this uncommon disease.

Multiple hyperdontia: Report of an unusual case.

Supernumerary teeth are an infrequent developmental anomaly that can appear in any area of the dental arch and can affect any dental organ. Multiple supernumerary teeth, or hyperdontia, is rare in people with no other associated diseases or syndromes. Conditions commonly associated with hyperdontia include cleft lip and palate, trichorhinophalangeal syndrome, cleidocranial dysplasia, and Gardner's syndrome. A black girl, aged 11 years 8 months, came for consultation; radiographs showed 81 teeth: 18 deciduous, 32 permanent, and 31 supernumerary. The main concern initially was to determine whether she was syndromic, and she was referred to a geneticist. G banding analysis showed pericentric inversion of chromosome 9; the chromosome formula was 46, XX, inv (9) (p13q21). Orthodontic treatment for this patient will be a clinical challenge because of the great number of teeth to be extracted and the alterations in the shapes of the teeth. Treatment goals should be established by a multidisciplinary team, where oral surgeon, orthodontist, periodontist, and prosthodontist come together to solve a medical and dental puzzle, eliminating the pieces that do not fit and searching for new ones to obtain an occlusion that will give the patient physiologic conditions of normality and esthetic satisfaction.

Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.

SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases.

Cleidocranial dysplasia: a family report.

A 10-year-old girl presented with a chief complaint of many unerupted teeth. Complete clinical and radiological examination of this patient confirmed the diagnosis of cleidocranial dysplasia (CCD). Her father also presented similar features with a lesser clinical severity. CCD is an autosomal-dominant heritable skeletal disease caused by heterozygous mutations in the osteoblast-specific transcription factor RUNX2 gene. Failure of tooth eruption is probably mainly due to this mutated gene in CCD patients. Interdisciplinary treatment approach is obligatory for rehabilitation of these patients. In confirmed cases, genetic counseling for family planning should certainly be advised.

The role of Cone beam CT in the evaluation and management of a family with Gardner's syndrome.

Gardner's syndrome (GS) is a hereditary autosomal dominant disease of the colon that presents with extra-colonic manifestations such as osteomas, skin lesions and dental abnormalities. Osteomas are commonly found in the skull, jaws and the paranasal sinuses. We present a family of four sisters affected with GS with a wide range of anomalies. The role of Cone beam computed tomography (CBCT) in the early detection and evaluation of osteomas and dental anomalies with precise assessment of their relationship to adjacent anatomic structures is described here in detail. The careful interpretation of CBCT may be of a great value in surgical and orthodontic treatment planning in the presence of jaw lesions. Management of dental problems in GS may be challenging due to the presence of odontomas and increased bone density. A multidisciplinary approach in the management of GS can achieve the best treatment results.

Tercer molar ectópico impactado en zona retromolar: reporte de caso / Ectopic and impacted third molar in retromolar zone: a case report

El desarrollo dentario resulta de una complicada interacción entre el epitelio oral y el tejido mesenquimático subyacente. La interacción anormal de tejidos en este período podría resultar en el desarrollo y erupción de un diente ectópico. Terceros molares incluidos son una de las patologías más frecuentes encontradas en cirugías oral y maxilofacial. Su evaluación generalmente es radiográfica, y los de ubicación mesioangular son los más prevalentes en la mandíbula. El presente reporte muestra un caso clínico de tercer molar incluido en la región retromolar mandibular. El diagnóstico se efectuó durante una evaluación por medio del análisis de una ortopantomografía en un paciente de sexo femenino de 51 años de edad. La pieza estaba ubicada en la zona retromolar mandibular derecha inmediatamente subcortical. Dado que se encontraba asintomática, sin signos radiográficos ni clínicos de patología, no fue indicada la exodoncia; sin embargo, es importante considerar esta variación anatómica y una posible resolución quirúrgica de ella ante la posible rehabilitación protésica del área.

Tooth develop results of several interactions between oral epithelium end underlying mesenchymatic tissue during odontogenesis. Abnormal relation of tissues could result in develop and eruption of an ectopic tooth. Impacted third molars are a frequent pathology in oral and maxillofacial surgery, it evaluation is commonly radiographic, and the most frequent position in jaw bone is mesioangular. This report wants to show an impacted third molar in mandibular retromolar region. Diagnosis was done through a orthopantomographic study during a clinical evaluation of 51 years of age female patient. Teeth was found sub cortical of right retromolar zone. Considering patient did not related or shown clinical signs of pathology, and radiograph neither had disease compatible signs, was resolved do not proceed to extraction. However, is important to consider this anatomical variation and a possible surgical resolution if a prosthetic rehabilitation of this area.

Familial occurrence of nonsyndromal multiple supernumerary teeth. A rare condition.

The occurrence of multiple supernumerary teeth is a rare phenomenon and is often found in association with syndromes such as cleidocranial dysplasia, Gardners syndrome, or cleft lip and palate. Only a few examples of nonsyndromal multiple supernumerary teeth have been reported in the literature. There is a predilection for the mandible and in the premolar area followed by the molar and anterior regions. This article reports the presence of nonsyndromal multiple supernumerary teeth involving both jaws in children and in their mothers. The clinical and radiographic appearance of the anomalies and treatment modalities are discussed.

Osteoglophonic dysplasia: dental and orthodontic implications.

AIMS AND OBJECTIVES: Documentation of dental and orthodontic implications of osteoglophonic dysplasia (OGD). SETTINGS AND PARTICIPANTS: Case report describing oral and dental manifestations of a female with OGD, aged 39 years, who was first documented three decades ago. RESULTS: This rare genetic disorder manifests with gross stunting of stature, associated with severe craniofacial malformation and multiple unerupted teeth. Radiographically, multiple lucent lesions were present in the tubular bones and mandible as well as several impacted teeth. CONCLUSION: We concluded that prosthetic dental replacement in this patient would be difficult because of the distorted jaw relationship and large alveolar ridges. Equally, craniofacial reconstruction might be compromised by obstruction of the nasal airways, difficulty in intubation and postoperative respiratory problems.

Dental findings and rehabilitation in familial osteodysplasia (Anderson type): a case report.

Familial osteodysplasia is a disorder of osteogenesis with an autosomal recessive pattern of inheritance which predominantly affects facial bones. No recent case had been reported, particularly from a dental point of view since the syndrome was first described by Anderson et al (JAMA 1972;220:1687-93). A 23-year-old male with familial osteodysplasia was presented in maxillofacial and dental aspects with clinical and radiological manifestations including malocclusion, abnormal teeth alignment, impacted teeth, shape disturbances including uncompleted coronal formation, root shortening with bulbous form, high angled mandible and elongation of the corpus of mandible. Recognition of the syndromal features prior to any dental intervention is of paramount importance because of increased inclination to spontaneous mandibular fractures. Hence, no surgical intervention was performed for impacted teeth. Following the extractions of severely mobile teeth, a definitive restoration was fabricated as distal-extension removable partial dentures with conus crown telescopic system. The aesthetic and functional outcome was satisfactory for the patient. In conclusion, dentists appear to play an important role in the recognition of familial osteodysplasia, based on maxillofacial and dentoalveolar findings. Awareness of the syndromal features, especially of spontaneous fractures, would detect the limitations for dental interventions and treatment planning.

[Oral and maxillofacial manifestations of familial adenomatosis polyposis. Gardner's syndrome]. / Orale en maxillofaciale afwijkingen bij familiaire adenomateuze polyposis. Het syndroom van Gardner.

Patients suffering from familial adenomatosis polyposis develop multiple pre-malignant gastrointestinal polyps and are at high risk of developing colon cancer. In addition extra-intestinal manifestations are observed frequently. The combination of extra-intestinal manifestations and familial adenomatosis polyposis is named Gardner's syndrome. An early diagnosis of this disease is important because it could mean a better prognosis for the patient. This review describes the oral and maxillofacial symptoms of FAP, and its potential implications for dental treatment.

Congenital tooth anomalies and malocclusions: a genetic link?

The aim of the present study was to investigate putative relationships between different malocclusions such as Class III and Class II division 1, and congenital tooth anomalies. Two-hundred Class III and 215 Class II division 1 patients were examined for the presence of any of the following congenital tooth anomalies: maxillary incisor hypodontia, maxillary canine impaction, transpositions, supernumerary teeth, and tooth agenesis. Their occurrence rates were then calculated as a percentage of the total sample and were compared for statistical differences. The results revealed no statistical difference (P > 0.05) in the occurrence rates of upper lateral incisor agenesis, peg-shaped laterals, impacted canines, or supernumerary teeth between the Class III and the Class II division 1 malocclusions. When the occurrence rate of all congenital tooth anomalies was compared between the two malocclusions, Class III subjects showed significantly higher rates (P < 0.05). Comparison with published surveys on general populations showed similar occurrence rates. It can be concluded that subjects with Class III and Class II division 1 malocclusions show patterns of congenital tooth anomalies similar to those observed in the general population. Congenital tooth anomalies may represent another criterion for the study of malocclusion, with respect to their origin and development.