Risk prediction model of impacted supernumerary tooth-associated root resorption in children based on cone-beam computed tomography analysis: a case control study.

BACKGROUND: External surface resorption is pressure-induced resorption and occurs on the external surface of the root, pressure exerted by impacted teeth, is common causes of external surface resorption. Predictive risk factors of impacted supernumerary tooth-associated root resorption (ISTARR) mentioned in this article include supernumerary teeth and patient factors. To investigate the risk factors of impacted supernumerary tooth-associated root resorption and predict the incidence of root resorption. METHODS: This restrospective study enrolled 324 patients with impacted supernumerary tooth. All Cone-Beam Computed Tomography (CBCT) data and patient information were divided into two groups (without tooth root resorption and with root resorption). CBCT images and patient information (age and gender) of 133 patients had adjacent tooth root resorption and 191 did not. seven variables were analysed using binary logistic regression. RESULTS: Individual analysis of potential risk factors showed that age, crown mesiodistal direction, root formation, and odontotheca of the impacted supernumerary tooth were associated significantly with ISTARR. Binary logistic regression showed that impacted supernumerary tooth with odontotheca (Odd Ratio = 2.926), the crown is in the middle (Odd Ratio = 1.446), located at the middle third of the adjacent tooth root (Odd Ratio = 1.614), complete root development (Odd Ratio = 1.334), and patient's age (Odd Ratio = 1.261) were significantly associated with ISTARR risk. CONCLUSIONS: The risk factors of root resorption can be detected and predicted early according to the features of supernumerary tooth and patient's age. Still, more prospective studies with larger sample size are needed to validate the result.

Apoptotic Extracellular Vesicles from Supernumerary Tooth-Derived Pulp Stem Cells Transfer COL1A1 to Promote Angiogenesis via PI3K/Akt/VEGF Pathway.

Purpose: Angiogenesis is a tightly controlled process that initiates the formation of new vessels and its dysfunction can lead to life-threatening diseases. Apoptotic extracellular vesicles (ApoEVs) have emerged as a proangiogenic agent with high safety and isolation efficiency profile, and ApoEVs from supernumerary tooth-derived pulp stem cells (SNTSC-ApoEVs) have their unique advantages with an easily accessible parental cell source and non-invasive cell harvesting. However, the detailed characteristics of SNTSC-ApoEVs are largely unknown. This study aimed to investigate the proangiogenic capacity and function molecule of SNTSC-ApoEVs. Methods: SNTSC-ApoEVs were isolated and characterized. In vitro effects of SNTSC-ApoEVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8, wound healing, transwell, and tube formation assays. The mRNA and protein levels of proangiogenic genes were quantified by qRT-PCR, Western blot, and immunofluorescence analysis. A Matrigel plug model was established in 6-week-old male nu/nu mice for one week, and the in vivo impact of SNTSC-ApoEVs on micro-vessel formation was assessed by histological analysis. Proteomic analysis and RNA sequencing were performed to explore the active ingredients and underlying mechanisms. Results: SNTSC-ApoEVs enhanced the proliferation, migration, and angiogenesis of HUVECs in vitro. In the Matrigel plug model in vivo, SNTSC-ApoEVs promoted CD31-positive luminal structure formation. Apart from expressing general ApoEV markers, SNTSC-ApoEVs were enriched with multiple proteins related to extracellular matrix-cell interactions. Mechanistically, SNTSC-ApoEVs transferred COL1A1 to HUVECs and promoted endothelial functions by activating the PI3K/Akt/VEGF cascade. Conclusion: SNTSC-ApoEVs can promote angiogenesis by transferring the functional molecule COL1A1 and activating the PI3K/Akt/VEGF pathway, making SNTSC-ApoEVs a promising strategy for the treatment of angiogenesis-related diseases.

Treatment and genetic analysis of multiple supernumerary and impacted teeth in an adolescent patient.

BACKGROUND: Multiple supernumerary teeth, combined with numerous impacted teeth, can lead to various malocclusions, posing significant treatment challenges. While certain genes associated with syndromic cases of multiple supernumerary and impacted teeth have been identified, the etiologies of non-syndromic cases still largely remain elusive. CASE PRESENTATION: Here, we report a treatment of a 12-year-old boy who presented with 10 supernumerary teeth and 6 impacted teeth, accompanied by a genetic analysis to explore the underlying etiology. During the treatment, fifteen teeth were extracted, and various skilled techniques, including the closed-eruption technique and the application of by-pass arches, were utilized. Post-treatment, traction was successful for all the impacted teeth, without any tooth mobility or reduction in gingival height. Space closure, well-aligned teeth, and excellent functional occlusion were achieved. Furthermore, comprehensive genetic analysis was conducted through whole-exome sequencing on the patient and his parents, which revealed a potential link between the patient's numerous supernumerary teeth and abnormal mineralization. Notably, the p.Ser496Pro variant in the TCF7L2 gene was identified as a potential candidate variant in this patient. CONCLUSIONS: Overall, our findings not only report the treatment of a rare case involving multiple supernumerary and impacted teeth but also offer valuable insights into the molecular basis of supernumerary teeth.

Comparative proteomic analysis of dental pulp from supernumerary and normal permanent teeth.

OBJECTIVES: To obtain and compare the protein profiles of supernumerary and normal permanent dental pulp tissues. MATERIALS AND METHODS: Dental pulp tissues were obtained from supernumerary and normal permanent teeth. Proteins were extracted and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS-MS). Protein identification and quantification from MS data was performed with MaxQuant. Statistical analysis was conducted using Metaboanalyst to identify differentially expressed proteins (DEPs) (P-value < 0.05, fold-change > 2). Gene Ontology enrichment analyses were performed with gProfiler. RESULTS: A total of 3,534 proteins were found in normal dental pulp tissue and 1,093 in supernumerary dental pulp tissue, with 174 DEPs between the two groups. This analysis revealed similar functional characteristics in terms of cellular component organization, cell differentiation, developmental process, and response to stimulus, alongside exclusive functions unique to normal permanent dental pulp tissues such as healing, vascular development and cell death. Upon examination of DEPs, these proteins were associated with the processes of wound healing and apoptosis. CONCLUSIONS: This study provides a comprehensive understanding of the protein profile of dental pulp tissue, including the first such profiling of supernumerary permanent dental pulp. There are functional differences between the proteomic profiles of supernumerary and normal permanent dental pulp tissue, despite certain biological similarities between the two groups. Differences in protein expression were identified, and the identified DEPs were linked to the healing and apoptosis processes. CLINICAL RELEVANCE: This discovery enhances our knowledge of supernumerary and normal permanent pulp tissue, and serves as a valuable reference for future studies on supernumerary teeth.

Genetic Variants in KCTD1 Are Associated with Isolated Dental Anomalies.

KCTD1 plays crucial roles in regulating both the SHH and WNT/ß-catenin signaling pathways, which are essential for tooth development. The objective of this study was to investigate if genetic variants in KCTD1 might also be associated with isolated dental anomalies. We clinically and radiographically investigated 362 patients affected with isolated dental anomalies. Whole exome sequencing identified two unrelated families with rare (p.Arg241Gln) or novel (p.Pro243Ser) variants in KCTD1. The variants segregated with the dental anomalies in all nine patients from the two families. Clinical findings of the patients included taurodontism, unseparated roots, long roots, tooth agenesis, a supernumerary tooth, torus palatinus, and torus mandibularis. The role of Kctd1 in root development is supported by our immunohistochemical study showing high expression of Kctd1 in Hertwig epithelial root sheath. The KCTD1 variants in our patients are the first variants found to be located in the C-terminal domain, which might disrupt protein-protein interactions and/or SUMOylation and subsequently result in aberrant WNT-SHH-BMP signaling and isolated dental anomalies. Functional studies on the p.Arg241Gln variant are consistent with an impact on ß-catenin levels and canonical WNT signaling. This is the first report of the association of KCTD1 variants and isolated dental anomalies.

Third molar agenesis in individuals with supernumerary teeth.

OBJECTIVES: To explore the association between third molar agenesis and supernumerary tooth formation in a white-European population. MATERIALS AND METHODS: A record review in various orthodontic clinics identified 380 eligible white-European individuals, half of whom had non-syndromic permanent supernumerary teeth (122 males and 68 females, totalling 244 supernumerary teeth; median age: 13.1, iqr: 1.5 years), and the other half were age- and sex-matched controls with full dentition, excluding the third molars. Tooth sequences were identified in panoramic radiographs. RESULTS: In the supernumerary group, approximately 80% of the individuals had a single supernumerary tooth, followed by those having two additional teeth. In both groups, there was no sexual dimorphism in third molar agenesis severity. The prevalence of third molar agenesis in the supernumerary group was similar to that of the control group (28/190 = 14.7% in both groups; p = 1.0). In total, 53 third molars were missing in the supernumerary group (n = 190) compared to 67 in the control group (n = 190; p = .862). The ratio of bilateral to unilateral third molar agenesis was significantly lower in the supernumerary group than in the control group (1.0 vs. 3.7, respectively; p = .026). CONCLUSION: The presence of supernumerary teeth did not significantly alter the likelihood of third molar agenesis or its severity. Bilateral third molar agenesis was considerably less prevalent in individuals with supernumerary teeth compared to controls. The present novel findings have important clinical and developmental implications.

Quistes Dentígeros Asociados a Mesiodens. Revisión de la Literatura a Propósito de Dos Casos

El mesiodens es el diente supernumerario que se origina en la premaxila, siendo considerado el más prevalente o el más diagnosticado debido a las numerosas alteraciones que producen y que incluyen malposición de los dientes permanentes, formación de diastemas, retraso en la erupción de los incisivos anteriores superiores, y formación de quistes. La etiología de los mesiodens no está completamente comprendida, aunque se piensa que pueda deberse a la proliferación de la lámina dental u otros factores genéticos. El diagnóstico generalmente es tardío debido a que la mayoría permanece sin erupcionar, pudiendo generar complicaciones dentomaxilares que finalmente son el motivo de consulta de los pacientes. El quiste dentígero es un quiste odontogénico del desarrollo asociado a la corona de un diente incluido, numerario o supernumerario y su tratamiento es quirúrgico. El diagnóstico temprano y la planificación del tratamiento debe considerar una anamnesis minuciosa, un examen clínico e imágenes 3D. La cirugía debe consistir en la desinclusión del diente causal, la exéresis y legrado de la lesión, con o sin regeneración ósea inmediata del lecho quirúrgico con injerto. Se presentan dos casos de quiste dentígero asociado a un mesiodens que se diagnosticaron como hallazgo radiográfico. El plan de tratamiento consistió en evaluación y tratamiento endodóntico de los dientes desvitalizados, enucleción y legrado del quiste, junto a la desinclu sión del diente supernumerario, y seguimiento clínico y radiográfico en el largo plazo.

Mesiodens is the supernumerary tooth that originates in the premaxilla, considered the most prevalent or, the most diagnosed due to the multiple alterations that produce and that include malposition of the permanent teeth, formation of gaps, delayed eruption of the upper anterior incisors and cyst formation. The etiology of mesiodens is not fully established, although it is thought that it may be due dental lamina alteration or other genetic factors. Diagnosis is usually late because most remain unerupted, and can generate dentomaxillary complications that are ultimately the reason for patient consultation. The dentigerous cyst is a developmental odontogenic cyst associated with the crown of an included, numerary or supernumerary tooth and its treatment is surgery. Early diagnosis and treatment planning should consider a careful history, clinical examination, and 3D imaging. The surgery must consist of the disinclusion of the offending tooth, the exeresis and curettage of the lesion, with or without immediate bone regeneration of the surgical bed with a graft. Two cases of a dentigerous cyst associated with a mesiodens that were diagnosed as a radiographic finding are presented. The treatment plan consisted in evaluation and endodontic treatment of devitalized teeth, enucleation and curettage of the cyst, together with the disinclusion of the supernumerary tooth, and long-term clinical and radiographic follow-up.

Fusion of a maxillary third molar with a supernumerary fourth molar: A case report.

Key Clinical Message: Dental fusion should be included in differential diagnosis when panoramic radiograph reveals changes in tooth shape or size. The use of specialized dental photographic techniques can augment the dentists' knowledge and awareness of such conditions. Abstract: Dental fusion of impacted teeth may show up as a change in tooth shape and size on the first radiographic examination. This report presents an impacted maxillary third molar fused with a peg-like distomolar in a 20-year-old male. The patient presented with symptoms of localized periodontitis distal to the second molar, and radiographic examination revealed abnormal dental structure of the third molar. Surgical extraction of the impacted molar was the treatment of choice. The final diagnosis of fusion was based on data from ex vivo CBCT, photographs of the extracted tooth, and extracted tooth's sections using polarizing filters. Two-dimensional radiographs may conceal special dental anatomies. Visualization of such cases using CBCT and dental photography serves to educate dentists and reduce postoperative complications. Knowledge and awareness of possible dental abnormalities are of utmost importance for successful treatment planning.

Harmonizing Dentofacial Balance: A Comprehensive Exploration of Class 1 Malocclusion Resolution With Impacted Maxillary Central Incisor Management.

Permanent maxillary central incisor impaction is generally a rare phenomenon. Because the anterior teeth have a huge impact on a patient's facial aesthetics, missing anterior teeth are of major concern to patients who seek orthodontic treatment. However, correcting this type of malocclusion poses a challenge to the orthodontist. This case report of a 16-year-old male patient with an impacted maxillary right central incisor takes us through a series of events that are necessary to treat this type of malocclusion. The presenting case also had an impacted supernumerary tooth which was the primary cause for permanent tooth impaction. A combined treatment approach is usually needed to manage this type of case involving both the orthodontist and the surgeon.

Unveiling the Journey: A Case Report of Managing an Impacted Central Incisor.

Although impaction of the maxillary permanent central incisor is uncommon in dentistry due to its significance to facial aesthetics which are challenging to treat. To abstain from the consequences related to aesthetic and functional occlusion, early detection of an impacted central incisor is imperative. This case report describes a male patient, aged 22 years, who had an impacted central incisor tooth in the maxillary anterior region. A surgery was performed to remove the impacted supernumerary tooth that was preventing the eruption of the central incisor. Using a combination of surgical exposure and orthodontic force, the impacted right maxillary central incisor was relocated to its proper occlusion in the dental arch.

Effect of maxillary anterior supernumerary tooth extraction on the underlying malocclusion.

INTRODUCTION: Orthodontic discrepancies are a common finding in patients with supernumerary teeth (ST). The presence of a ST can cause a number of orthodontic discrepancies, including delayed eruption or retention of adjacent teeth, crowding, spacing, and abnormal root formation. The aim of the present study was to assess the effect of extraction of an anterior supernumerary tooth on the underlying orthodontic discrepancies without additional treatment for a 6-month period. METHODS: This was a prospective, longitudinal, observational, study. It included 40 participants with orthodontic malocclusions due to maxillary anterior supernumeraries. We examined the changes in the crowding and excessive space in the anterior and posterior segments on cast models. RESULTS: In the group that presented with crowding, a statistically significant decrease of 0.95 ± 0.17 mm (P < 0.001) was found between T0 and T1. Of the participants, three exhibited full self-correction. The excessive space at T0 (3.06 mm) decreased by 1.78 ± 0.19 mm to T1 (1.28 mm) in the anterior segment. Seven participants showed full self-correction of the diastemas after the 6-month observation period. CONCLUSION: The results imply that orthodontic treatment can be postponed for at least 6 months after the extraction of the supernumerary tooth as potential self-correction can be expected. This natural alleviation of the malocclusions may make the orthodontic treatment simpler, shorten the treatment time and decrease overall appliance wear time.

Exodoncia de premolar inferior supernumerario con posterior colocación de Fibrina Rica en Plaquetas y Leucocitos (L-PRF)

Los dientes supernumerarios son una anomalía odontogénica, consiste en aumento del número dentario con respecto a la cantidad normal. La Fibrina rica en Plaquetas y Leucocitos (L-PRF) es una matriz rica en plaquetas y glóbulos blancos, que promueve la curación y regeneración de los tejidos. La exodoncia de un tercer premolar inferior supernumerario con posterior colocación de membrana de L-PRF. Paciente de sexo masculino de 27 años de edad con un probable premolar supernumerario por lingual. Se programó la cirugía incluyendo L-PRF. Se realizó extracción de sangre para preparar la membrana de L-PRF, anestesia, incisión lineal, despegamiento mucoperióstico, osteotomía, exodoncia, tratamiento del lecho quirúrgico colocando la membrana de L-PRF y sutura interdental. Se prescribió medicación antibiótica, antiinflamatoria y analgésica. La técnica con L-PRF es sencilla y económica. Los resultados postoperatorios fueron favorables, observándose una buena cicatrización, ausencia de dolor, edema o infección.

Supernumerary teeth are an odontogenic anomaly, involving an increase in the number of teeth compared to the normal amount. Platelet-Rich Fibrin (L-PRF) is a matrix rich in platelets and white blood cells that promotes tissue healing and regeneration. The Extraction of a supernumerary lower third premolar followed by placement of L-PRF membrane. A 27-year-old male patient with a probable lingual supernumerary premolar. Surgery was scheduled, including L-PRF. Blood was extracted to prepare the L-PRF membrane, followed by anesthesia, linear incision, mucoperiosteal detachment, osteotomy, extraction, treatment of the surgical site with L-PRF membrane placement, and interdental suturing. Antibiotic, anti-inflammatory, and analgesic medication was prescribed. The L-PRF technique is simple and cost-effective. Postoperative results were favorable, with good healing, absence of pain, swelling, or infection was observed.

Management of a supernumerary tooth fused to the labial surface of a permanent maxillary central incisor.

Key Clinical Message: Management of supernumerary teeth fused to the labial surface of permanent maxillary central incisors would require a multidisciplinary approach comprising of endodontic treatment, periodontal recontouring, and cosmetic composite restoration. Abstract: The reported cases of supernumerary teeth fused to the labial surface of maxillary central incisors are rare. Such cases need multidisciplinary approaches. Herein, management of a supernumerary tooth fused to the labial surface of a maxillary central incisor is reported. Due to the presence of a communication path between the root canal systems of the two fused teeth, root canal therapy was performed first for the maxillary left central incisor and the supernumerary tooth. The crown of the supernumerary tooth was then removed in a surgical setting while preserving the root to maintain the thin covering of alveolar bone and prevent future periodontal problems. Subsequently, an esthetic composite restoration was performed.

Supernumerary Tooth Patterns in Non-Syndromic White European Subjects.

Supernumerary teeth form at an incidence of about 3% in the population, with differences among races and various clinical consequences. Information on detailed patterns, and especially on white subjects, is scarce in the literature. Therefore, we aimed to investigate the patterns of non-syndromic permanent supernumerary teeth in a white European population. A record review was performed in different orthodontic clinics and identified 207 eligible individuals with 258 supernumerary teeth. Approximately 80% of the subjects had one supernumerary tooth, while 15% had two. Supernumerary tooth formation was more often evident in males (male/female: 1.65). However, there was no sexual dimorphism in its severity. The following pattern sequences, with decreasing prevalence order, were observed in the maxilla: 21 > 11 > 12 > 18 > 28 and in the mandible: 34 > 44 > 35 > 45 > 42. Supernumerary teeth were most often unilaterally present, without sexual dimorphism. In the maxilla, they were more often anteriorly present, whereas in the mandible, an opposite tendency was observed. Supernumerary teeth were consistently more often observed in the maxilla than in the mandible; 74% were impacted, 80% had normal orientation (13% horizontal, 7% inverted), and 53% had normal size. The present thorough supernumerary tooth pattern assessment enables a better understanding of this condition with clinical, developmental, and evolutionary implications.

Count Me in, Count Me out: Regulation of the Tooth Number via Three Directional Developmental Patterns.

Tooth number anomalies, including hyperdontia and hypodontia, are common congenital dental problems in the dental clinic. The precise number of teeth in a dentition is essential for proper speech, mastication, and aesthetics. Teeth are ectodermal organs that develop from the interaction of a thickened epithelium (dental placode) with the neural-crest-derived ectomesenchyme. There is extensive histological, molecular, and genetic evidence regarding how the tooth number is regulated in this serial process, but there is currently no universal classification for tooth number abnormalities. In this review, we propose a novel regulatory network for the tooth number based on the inherent dentition formation process. This network includes three intuitive directions: the development of a single tooth, the formation of a single dentition with elongation of the continual lamina, and tooth replacement with the development of the successional lamina. This article summarizes recent reports on early tooth development and provides an analytical framework to classify future relevant experiments.

An Unusual Case of Mesial Supplementary Lateral Incisor: A Case Report.

By definition, supplemental teeth are supernumerary teeth (ST) resembling adjacent teeth at the end of a tooth series and are well aligned in the arch. A case of the non-syndrome, supplemental type of supernumerary lateral incisor is presented, along with an unusual habit that was noted accidentally in the same child. In the present case, of the two lateral incisors, the mesial supplemental lateral incisor was causing an impaction of 11. In addition, the patient was aesthetically concerned. So, the decision was made to extract the supplemental tooth with altered morphology (mesial one) under local anesthesia even though, as per definition, the distal one is the supplementary tooth. And finally, to align the incisors by orthodontic treatment. Aim: A case of the non-syndrome, supplemental type of supernumerary lateral incisor is presented, along with an unusual habit of that was noted accidentally in the same child. Background: By definition, supplemental teeth are supernumerary teeth (ST) resembling adjacent teeth at the end of a tooth series and are well aligned in the arch. Case description: In the present case, of the two lateral incisors, the mesial supplemental lateral incisor was causing impaction of 11. In addition, the patient was aesthetically concerned. Conclusion: Decision was made to extract the supplemental tooth with altered morphology (mesial one) under local anesthesia even though, as per definition, the distal one is the supplementary tooth. And finally, to align the incisors by orthodontic treatment. Clinical significance: Decision-making regarding removal of tooth is quite baffling as a selective removal of the normal or the supplementary tooth may be required and it should be made after analyzing multiple factors. How to cite this article: Sojan M, Thakur S. An Unusual Case of Mesial Supplementary Lateral Incisor; A Case Report. Int J Clin Pediatr Dent 2023;16(3):518-521.

Prevalence of Dental Anomalies and Its Role in Sex Estimation among Children of Jazan Region, Saudi Arabia.

BACKGROUND: This study aimed to ascertain the prevalence of dental anomalies and their ability to estimate sex status. MATERIAL AND METHODS: This cross-sectional radiographic study was based on the evaluation of dental anomalies of Saudi children aged between 5 and 17 years. A total of 1940 orthopantomograms (OPG) were screened, of which 1442 were included. All the OPGs were digitally evaluated with ImageJ software. The demographic variables and dental anomaly findings were subjected to descriptive and comparative statistical analysis. Discriminant function analysis was conducted for sex estimation. p value < 0.05 was considered as significant. RESULTS: The mean age of the children in this study was 11.35 ± 0.28 years. At least one dental anomaly was detected in 161 children (11.17%), including 71 males and 90 females. Only 13 children (8.07%) presented with more than one anomaly. The most common dental anomaly detected was root dilaceration (47.83%) followed by hypodontia (31.68%). The least common dental anomaly was infraocclusion (1.86%). The sex prediction accuracy using discriminant function analysis was 62.9% (p < 0.01). CONCLUSION: The prevalence of dental anomalies was 11.17% with root dilaceration and hypodontia being the most common. The role of dental anomalies in sex estimation was found to be ineffective.

Heterozygous Variants in FREM2 Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas.

BACKGROUND: Supernumerary teeth refer to extra teeth that exceed the usual number of dentitions. A mesiodens is a particular form of supernumerary tooth, which is located in the premaxilla region. The objective of the study was to investigate the genetic etiology of extra tooth phenotypes, including mesiodens and isolated supernumerary teeth. METHODS: Oral and radiographic examinations and whole-exome sequencing were performed on every patient in our cohort of 122 patients, including 27 patients with isolated supernumerary teeth and 94 patients with mesiodens. A patient who had multiple supernumerary teeth also had odontomas. RESULTS: We identified a novel (c.8498A>G; p.Asn2833Ser) and six recurrent (c.1603C>T; p.Arg535Cys, c.5852G>A; p.Arg1951His, c.6949A>T; p.Thr2317Ser; c.1549G>A; p.Val517Met, c.1921A>G; p.Thr641Ala, and c.850G>C; p.Val284Leu) heterozygous missense variants in FREM2 in eight patients with extra tooth phenotypes. CONCLUSIONS: Biallelic variants in FREM2 are implicated in autosomal recessive Fraser syndrome with or without dental anomalies. Here, we report for the first time that heterozygous carriers of FREM2 variants have phenotypes including oral exostoses, mesiodens, and isolated supernumerary teeth.

Genetic Variants in Protein Tyrosine Phosphatase Non-Receptor Type 23 Are Responsible for Mesiodens Formation.

A mesiodens is a supernumerary tooth located in the midline of the premaxilla. To investigate the genetic cause of mesiodens, clinical and radiographic examination were performed on 23 family members of a two-generation Hmong family. Whole exome sequencing (WES) or Sanger sequencing were performed in 22 family members and two unrelated Thai patients with mesiodens. WES in the Hmong family revealed a missense mutation (c.1807G>A;p.Glu603Lys) in PTPN23 in seven affected members and six unaffected members. The mode of inheritance was autosomal dominance with incomplete penetrance (53.84%). Two additional mutations in PTPN23, c.2248C>G;p.Pro750Ala and c.3298C>T;p.Arg1100Cys were identified in two unrelated patients with mesiodens. PTPN23 is a regulator of endosomal trafficking functioning to move activated membrane receptors, such as EGFR, from the endosomal sorting complex towards the ESCRT-III complex for multivesicular body biogenesis, lysosomal degradation, and subsequent downregulation of receptor signaling. Immunohistochemical study and RNAscope on developing mouse embryos showed broad expression of PTPN23 in oral tissues, while immunofluorescence showed that EGFR was specifically concentrated in the midline epithelium. Importantly, PTPN23 mutant protein was shown to have reduced phosphatase activity. In conclusion, mesiodens were associated with genetic variants in PTPN23, suggesting that mesiodens may form due to defects in endosomal trafficking, leading to disrupted midline signaling.