Non-syndromic Oligodontia Research Articles

Functional Analysis of Ectodysplasin-A Mutations in X-Linked Nonsyndromic Hypodontia and Possible Involvement of X-Chromosome Inactivation.

Background Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndrome hypohidrotic ectodermal dysplasia or nonsyndromic tooth agenesis. The influence of EDA mutations on dentinogenesis and odontoblast differentiation has not been reported. The aim of this study was to identify genetic clues for the causes of familial nonsyndromic oligodontia and explore the underlying mechanisms involved, while focusing on the role of human dental pulp stem cells (hDPSCs). Materials and Methods Candidate gene sequences were obtained by PCR amplification and Sanger sequencing. Functional analysis was conducted, and the pathogenesis associated with EDA mutations in hDPSCs was investigated to explore the impact of the identified mutation on the phenotype. Capillary electrophoresis (CE) was used to detect X-chromosome inactivation (XCI) in the blood of female carriers. Results In this study, we identified an EDA mutation in a Chinese family: the missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with a mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with transfection of control EDA lentivirus. Mechanistically, mutant EDA inhibited the activation of the NF-κB pathway. The CE results showed that symptomatic female carriers had a skewed XCI with a preferential inactivation of the X chromosome that carried the normal allele. Conclusions In summary, we demonstrated that EDA mutations result in nonsyndromic tooth agenesis in heterozygous females and that, mechanistically, EDA regulates odontogenesis through the NF-κB signalling pathway in hDPSCs. Due to the large heterogeneity of tooth agenesis, this study provided a genetic basis for individuals who exhibit similar clinical phenotypes.

Novel MSX1 frameshift mutation in a Japanese family with nonsyndromic oligodontia

Congenital tooth agenesis is a common anomaly in humans. We investigated the etiology of human tooth agenesis by exome analysis in Japanese patients, and found a previously undescribed heterozygous deletion (NM_002448.3(MSX1_v001):c.433_449del) in the first exon of the MSX1 gene. The deletion leads to a frameshift and generates a premature termination codon. The truncated form of MSX1, namely, p.(Trp145Leufs*24) lacks the homeodomain, which is crucial for transcription factor function.

Consecutive tooth agenesis patterns in non-syndromic oligodontia.

Agenesis of two or more consecutive adjacent permanent teeth (consecutive tooth agenesis, CTA) is a serious manifestation of oligodontia requiring long-term, multi-disciplinary treatment. Therefore, the present study investigated the characteristics of the CTA pattern in orthodontic patients with non-syndromic oligodontia. Using panoramic radiographs, the number of agenetic permanent teeth excluding third molars in non-syndromic orthodontic patients was evaluated, and patients with six or more agenetic teeth (oligodontia group, n = 97) and with one to five agenetic teeth (hypodontia group, n = 107) were selected. The numbers of CTA including third molars in each quadrant and in each patient were compared between the groups. Each quadrant with CTA of patients was categorized into one of the following four types: (I) involves anterior teeth only; (II) involves posterior teeth only; (IIIA) includes anterior and posterior teeth; and (IIIB) separate in the anterior and posterior teeth. CTA in at least one quadrant was found in 91.8 and 4.7% of patients in the oligodontia and hypodontia groups, respectively. The highest frequency CTA patterns included agenesis of the first and second premolars and of the second and third molars in the oligodontia and hypodontia groups, respectively. In the oligodontia group, type IIIA was significantly more frequent in the maxillary than in the mandibular quadrant. Most oligodontia patients who visit orthodontic clinics have CTA. A rare but severe CTA pattern that continues from the anterior to posterior segments is more frequent in the maxillary than in the mandibular quadrant.

Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population.

Tooth agenesis is one of the most frequent congenital abnormalities found in the maxillofacial region. Oligodontia, a severe form of tooth agenesis, occurs as an isolated anomaly or as a syndromic feature. We performed whole exome sequencing analyses to identify causative mutation in a Japanese family with three affected individuals with non-syndromic oligodontia. After variant filtering procedures and validation by Sanger sequencing, we identified one missense mutation (c.668 C > T, p.Gly223Asp) in OPN3 at 1q43, encoding a photosensitive G-protein-coupled receptor (GPCR) expressed in various tissues including brain, liver, and adipose. This mutation was predicted to be pathogenic in silico and was not found in the public databases. We further examined 48 genetically unrelated cases by targeted sequencing of the OPN3 gene region and found one additional missense variant in this gene (c.768 C > T, p.Met256Ile) that was also predicted to be pathogenic. Localization of OPN3 protein by immunohistochemical analysis using mouse embryo revealed its specific expression in the tooth gems from bud to bell stages and their surrounding tissues. These results indicated that OPN3 was involved in non-syndromic oligodontia, which has made an anchoring point for clinical application including DNA diagnostics.

Identification of a novel mutation of the PAX9 gene and clinical treatment in a nonsyndromic oligodontia family

苏州大学附属第二医院口腔中心收治单纯型多数牙缺失1例，患者先天缺失恒牙16颗，其他系统无异常，其母与患者有相似表型。收集患者、患者父母及外祖父母外周血，提取DNA，采用PCR结合直接测序进行PAX9、MSX1、WNT10A、WNT10B、AXIN2和EDA等候选基因突变检测，PCR-Sanger测序发现PAX9基因的起始密码子存在1个杂合突变，即NM006194.3（PAX9）：c.2T>C（p.Met1Thr），使起始密码子突变为苏氨酸，患者母亲有相同突变，可能是该患者先天单纯型多数牙缺失的遗传致病原因。患者拔除口内滞留乳牙后进行正畸-修复序列治疗，疗效满意。.

Non-syndromic oligodontia in siblings: A spectrum of experience

Non-syndromic oligodontia, the agenesis of six or more teeth, has a prevalence of 0.14–0.25%. Genetic, epigenetic and environmental influences affect expression. Three brothers presented with agenesis of 14, 21 and 23 permanent teeth, respectively. They were medically well, with no relevant family history. Each case presented with caries, microdontia and attritive tooth surface loss. Comprehensive care was delivered in each case by undergraduate dental students. Individualized prevention and stabilization were completed before referral for multidisciplinary long-term planning. Primary dental care practitioners are instrumental in delivering preventive care and stabilizing the dentition in cases of dental anomaly, while sharing care with specialist teams. CPD/Clinical Relevance: An unusual presentation of non-syndromic oligodontia relevant to primary dental care practitioners who are likely to provide the first clinical contact and referral to the wider multidisciplinary team.

Sexual dimorphism of tooth agenesis patterns in non-syndromic oligodontia in Japanese patients

ObjectiveWide individual variation observed in tooth agenesis patterns in patients with non-syndromic oligodontia could be affected by sexual dimorphism. Therefore, the present study investigated sex-associated differences in tooth agenesis patterns in patients with non-syndromic oligodontia. DesignSubjects were 108 male (ages 7–46 years) and 184 female (ages 7–43 years) orthodontic patients missing ≥6 permanent teeth, excluding third molars. The number of agenetic teeth per patient, excluding third molars, and the prevalence of agenesis of each tooth type were evaluated using panoramic radiographic images. Rankings of the most common tooth agenesis patterns in the maxillary and mandibular arches were calculated. The number of agenetic teeth per patient was compared between sexes using the Mann–Whitney test. The prevalence of tooth agenesis for each tooth type was compared between sexes using the χ2 and Fisher's exact tests with Bonferroni correction. ResultsNo significant sex difference in the distribution of the number of agenetic teeth was observed. The prevalence of agenesis of the maxillary second premolars was significantly higher in females (P < 0.007) and the prevalence of agenesis of the mandibular central incisors was significantly higher in males (P < 0.007). Sexual dimorphism was observed in the highly ranked tooth agenesis patterns. ConclusionsNo significant difference in the severity of tooth agenesis was observed between sexes; however, sexual dimorphism was observed in the tooth agenesis patterns of patients with non-syndromic oligodontia. Although various tooth agenesis patterns were identified, sex-specific tendencies suggest that categories can be utilized in future epidemiologic research and planning.

Novel MSX1 variants identified in families with nonsyndromic oligodontia

The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel MSX1 heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.

Interdisciplinary management of nonsyndromic tooth agenesis in the digital age

Background and OverviewTooth agenesis is the most common congenital condition affecting the oral cavity. This condition can involve single or multiple missing teeth. Severe forms of tooth agenesis are best managed by a team of specialists, as they can be daunting for a single provider. Case DescriptionAs the goal of most patients is to replace missing teeth to improve cosmesis and function, a prosthodontist or restorative dentist plays a major role in the team’s effort. Although diagnostic skills and careful planning are still the mainstay of this treatment, digital technology and modern materials can greatly facilitate implementation of the treatment plan. The authors present a case of a patient with nonsyndromic oligodontia who had a deficient occlusal vertical dimension that was treated by means of an interdisciplinary approach. The management included a combination of orthodontics, fixed and removable prosthodontics, and oral surgery. Conclusions and Practical ImplicationsWhen treating patients with complex congenital tooth anomalies, the prosthodontist or restoring dentist is well positioned to take the lead and orchestrate treatment of the patient.

Functional study of novel PAX9 variants: The paired domain and non-syndromic oligodontia.

To investigate pathogenic variants of the paired box 9 (PAX9) gene in patients with non-syndromic oligodontia, and the functional impact of these variants. Whole exome sequencing and Sanger sequencing were utilized to detect gene variants in a cohort of 80 patients diagnosed with non-syndromic oligodontia. Bioinformatic and conformational analyses, fluorescence microscopy and luciferase reporter assay were employed to explore the functional impact. We identified three novel variants in the PAX9, including two frameshift variants (c.211_212insA; p.I71Nfs*246 and c.236_237insAC; p.T80Lfs*6), and one missense variant (c.229C>G; p.R77G). Familial co-segregation verified an autosomal-dominant inheritance pattern. Conformational analyses revealed that the variants resided in the paired domain, and could cause corresponding structural impairment of the PAX9 protein. Fluorescence microscopy showed abnormal subcellular localizations of frameshift variants, and luciferase assay showed impaired downstream transactivation activities of the bone morphogenetic protein 4 (BMP4) gene in all variants. Our findings broaden the spectrum of PAX9 variants in patients with non-syndromic oligodontia and support that paired domain structural impairment and the dominant-negative effect are likely the underlying mechanisms of PAX9-related non-syndromic oligodontia. Our findings will facilitate genetic diagnosis and counselling, and help lay the foundation for precise oral health therapies.

Comparative analysis of rare EDAR mutations and tooth agenesis pattern in EDAR- and EDA-associated nonsyndromic oligodontia.

Nonsyndromic oligodontia is a rare congenital anomaly. Mutations in the ectodysplasin A receptor (EDAR) gene are the primary cause of hypohidrotic ectodermal dysplasia but are rarely reported in nonsyndromic oligodontia. This study investigated EDAR mutations in multiplex nonsyndromic oligodontia and comparatively analyzed the EDAR- and EDA-related tooth agenesis patterns. Mutation screening was carried out using whole-exome sequencing and familial segregation. Evolutionary conservation and conformational analyses were used to evaluate the potential pathogenic influence of EDAR mutants. EDAR mutations were found to occur in 10.7% of nonsyndromic oligodontia cases. We reported seven heterozygous mutations of EDAR, including five novel mutations (c.404G>A, c.871G>A, c.43G>A, c.1072C>T, and c.1109T>C) and two known mutations (c.319A>G and c.1138A>C). Genotype-phenotype correlation analysis demonstrated that the EDAR-related tooth agenesis pattern was markedly different from EDA. The mandibular second premolars were most frequently missing (57.69%) in EDAR-mutated patients. Our results provide new evidence for the genotypic study of nonsyndromic oligodontia and suggest that EDAR haploinsufficiency results in nonsyndromic tooth agenesis. Furthermore, the distinct pattern between EDAR- and EDA-related tooth agenesis can be used as a guide for mutation screening during the clinical genetic diagnosis of this genetic disorder.

Numerous anomalies of teeth with concomitant nonsyndromic oligodontia in primary and permanent dentition: A rare case report

Aim: The case report aimed at reporting a rare case of numerous morphological anomalies of teeth with concomitant nonsyndromic oligodontia in primary and permanent dentition in the oral cavity. Background: Oligodontia is agenesis of numerous teeth preferably missing more than six teeth in the oral cavity, affects both primary and permanent dentition, and is commonly associated with ectodermal dysplasia or specific abnormalities. Agenesis of the primary teeth is rare, especially of the primary canines. The exact etiology is unknown. Case description: This paper reports a very rare case of an 8-year-old boy with multiple morphological anomalies of teeth, with missing primary canines, and 19 permanent teeth at 8 years of age, later followed up from 11 to 15 years. This paper discusses the prevalence, etiology, and management of oligodontia which was not associated with any syndrome like Van Der Woude, Reiger syndrome as it usually is, because the patient did not exhibit any of the associated findings with any syndrome, thereby making it rare of the rare cases. Conclusion: A rare case report of nonsyndromic oligodontia with multiple congenitally missing primary and permanent teeth associated with morphological anomalies of the teeth and without the absence of any systemic disorders or syndromes is presented. Clinical Significance: Since oligodontia is always associated with ectodermal dysplasia or other syndromes, recognizing cases without associated syndromes which are necessary to evaluate any other underlying factors. Thus, the incidence of oligodontia which usually varies from 0.08% to 0.16% citing this case report falls into that 1% making it rare.

An unwonted case report of nonsyndromic oligodontia

Dental agenesis is a common developmental anomaly that affects approximately 20% of the population and results in a reduction of the number of teeth present in the oral cavity. Very rarely, more than one anomaly caused due to varying local etiological factors are seen in one patient. The aetiology of dental agenesis may be attributed to either environmental or genetic causes. Environmental factors include, different types of traumas to the alveolar processes, rubella, radiotherapy, use of chemical substances or drugs, as thalidomide and chemotherapy and disturbances in the innervations of the jaw. The absence of teeth is a clinical and public health problem, since the patients in these conditions may present several signs and symptoms as masticatory problems, malocclusion, problems in articulating words, and also the aesthetics may be compromised. These complications may affect self-esteem, behaviour pattern, and social life of these patients. Regarding the diagnosis of oligodontia, it is normally based on radiographic evidence and routine clinical examination, detecting absence of teeth or delayed eruption of them. The panoramic radiography is the most indicated for the diagnosis and study of agenesis, due to this radiographic exam register all maxilla-mandibular regions as well as the development of the tooth germ of the patient with minimal radiation. The motive of this article is to report a case of multiple local etiological factors as the cause of malocclusion and the interceptive management of the case, to prevent aesthetic, functional and psychological problems.

Cephalometric Measurements Of Non-Syndromic Oligodontia In Early Dental Age In A Japanese Population.

PurposeOligodontia significantly affects oral function and esthetics. Recognition of skeletal and dental patterns may aid in proper diagnosis and development of appropriate interventions. The aim of this study was to analyze skeletal and dental patterns for pre-adolescent patients with a diagnosis of oligodontia.Patients and methodsThis study included 19 oligodontia patients (age: 9.5±1.3, Hellman’s developmental stage IIIA~IIIB) along with a control group that comprised of 19 participants (age: 9.9±1.6) without any skeletal disharmony or congenitally missing teeth, with an Angle class I relationship and general crowding. Average cephalometric measurements among the oligodontia group were compared to the control group. The correlation between number of congenitally missing teeth (CMT) and each measurement was investigated. Skeletal measurements for both male and female patients in the oligodontia group and the control group were also compared.ResultsNo significant difference between the experimental and the control group was observed with respect to skeletal angular and linear measurements, except the gonial angle. Differences in dental pattern measurements were observed. The oligodontia group had significantly smaller Mo-Ms and Is-Mo than the control group (p<0.01). No correlation was detected between severity of oligodontia (number of CMT) and skeletal measurement except for SNB (R=−0.4). For females with oligodontia, Mo-Ms (eruption of maxillary first molar) and Is-Mo (mesial location of maxillary first molar) significantly differed from females in the control group (p<0.01). In contrast, no differences in Mo-Ms or Is-Mo were detected for male patients when oligodontia and control group were compared.ConclusionAmong pre-adolescent Japanese patients with oligodontia in Hellman’s developmental age IIIA~IIIB, no significant differences in skeletal characteristics were established when compared to the control group. However, tooth position of maxillary first molars indicated smaller vertical descent and mesial shift, which may suggest weak maxillary vertical development.

Tooth agenesis patterns in Japanese orthodontic patients with nonsyndromic oligodontia.

Tooth agenesis is the most common dental anomaly in humans and is often found in orthodontic patients. However, severe tooth agenesis (oligodontia) is rare and its characteristics are poorly understood. This study aimed to investigate tooth agenesis patterns of Japanese orthodontic patients with nonsyndromic oligodontia. Panoramic radiographs of 228 orthodontic patients (141 females, 87 males) with nonsyndromic oligodontia were selected and permanent tooth agenesis excluding third molars was evaluated. Influence of cutoff age was tested, tooth agenesis patterns for each quadrant were calculated, and antagonistic maxillary and mandibular quadrants were merged as the occluding tooth agenesis pattern. Full-mouth tooth agenesis patterns were also evaluated. The highest prevalence of tooth agenesis was observed in maxillary and mandibular second premolars, followed by maxillary first premolars. Prevalence of a symmetric pattern between right and left quadrants was significantly higher than matched patterns between maxillary and mandibular antagonistic quadrants. Among 456 possible tooth agenesis patterns, 51 and 49 patterns were observed for the maxillary and mandibular quadrants, respectively, but 215 patterns for the occluding patterns were observed. In addition, 180 full-mouth tooth agenesis patterns were observed in the 228 patients. Distinct characteristics in highly ranked patterns were observed compared with studies from other geographic areas, especially in the maxillary arch. Occluding and full-mouth tooth agenesis patterns showed wide variation, suggesting difficulty in orthodontic diagnosis.

Nonsyndromic familial Oligodontia in a 13 year old male: A case report

The most common oral developmental anomaly is dental agenesis which can be either in the form of Anodontia, Oligodontia, or Hyperdontia. This can occur either as an isolated finding or as part of a syndrome. Nonsyndromic Oligodontia is rare. Early intervention and prompt management improves quality of life. Here, we report a case of a 13-year-old male child with non-Syndromic Oligodontia without any association with specific systemic disease who allegedly had complete set of primary teeth but failed to develop complete permanent dentition.

Estimation of tooth agenesis risks between tooth types in orthodontic patients with non-syndromic oligodontia

Oligodontia, a severe type of hypodontia generally characterized as tooth agenesis of six or more permanent teeth excluding third molars, is known to have a multifactorial etiology and the characteristics of orthodontic patients are not fully understood. The aim of the present study was to investigate the risks of tooth agenesis between tooth types of permanent dentition in orthodontic patients with non-syndromic oligodontia. Panoramic radiographs of 292 orthodontic patients (184 females and 108 males) were obtained from one university-based orthodontic clinic and 79 private orthodontic clinics in Japan. Agenesis of permanent teeth excluding third molars was evaluated. Multiple logistic regression analysis was conducted to evaluate the risk of simultaneous tooth agenesis between all tooth type combinations. Significant symmetry of tooth agenesis was observed for all tooth types. Twenty-six tooth type combinations showed a significantly increased risk of simultaneous tooth agenesis [odds ratios (ORs): 1.99⬜14.51], and 15 tooth type combinations showed a significantly decreased risk of simultaneous tooth agenesis (ORs: 0.11⬜0.56). These findings suggest early detection to establish appropriate multidisciplinary treatment planning and prediction of the risk for tooth agenesis of non-syndromic oligodontia.

WNT10A mutations causing oligodontia

ObjectivesTo identify the molecular genetic etiology of the families with non-syndromic multiple missing permanent teeth (oligodontia). Materials and methodsGenomic DNA was isolated and measured, and whole-exome sequencing was performed. The obtained sequencing reads were aligned to the human reference genome and subsequently processed by a series of bioinformatics programs. Finally, short insertions/deletions and single nucleotide variations were annotated with dbSNP build 138. ResultsThe proband of family 1 was missing 14 permanent teeth, and the mutational analysis revealed compound heterozygousWNT10A mutations (c.364A > T and c.511C > T). Two affected individuals in family 2 were missing 20 and 12 permanent teeth, respectively, and compound heterozygous WNT10A mutations (c.364A > T and c.637G > A) were also identified. ConclusionsThis study reveals compound heterozygousWNT10A missense mutations in two families with non-syndromic oligodontia which will improve the understanding of odontogenesis and the pathogenesis related to WNT10A mutations.

Prevalence of WNT10A gene mutations in non-syndromic oligodontia.

Non-syndromic oligodontia is an infrequent clinical condition whose etiology is not yet completely understood being a wide spectrum of gene mutations described in concomitance with this severe form of tooth agenesis. Recently, multiple observations have linked up to 50% of cases with isolated hypodontia to mutations in the WNT10A gene. Here, we hypothesized that mutations in the WNT10A gene could also be present in families affected by non-syndromic oligodontia. All available patients with non-syndromic oligodontia (n = 20) treated at the Department of Orthodontics, University of Giessen, Germany between 1986 and 2013 as well as their family members were analyzed for mutations in the WNT10A gene. Mutation screening was positive in 50% of the 20 patients. The analysis revealed that the mutations 2:219755011(c.682T>TA)(p.F228I), 2:219754822(c.493G>GA)(p.G165R), 2:219754816(c.487C>CT)(p.R163W), and 2:219747090(c.321C>CA)(p.C107*), the novel missense mutation 2:219757676(c.937G/GT)(p.G313C), and the novel synonym variant 2:219754854(c.525C>CT)(p.H175H) were present. Multiple phenotypes are found in individuals presenting mutations in the WNT10A gene. Among them, the stop codon p.C107* as well as the biallelic p.F228I variants correlate with the most severe oligodontia phenotypes. In addition, we diagnosed the monoallelic mutations p.F228I, p.G165R, and p.G313C in healthy relatives with normal dentitions. A correct diagnosis of non-syndromic oligodontia is fundamental to discard a possible underlying pathology in which multiple tooth agenesis could be the most evidential clinical sign. Due to the wide spectrum of pathologies that are associated to mutations in the WNT10A gene, an extended genetic analysis of these individuals' relatives is also essential.

A novel mutation of MSX1 in oligodontia inhibits\xa0odontogenesis of dental pulp stem cells via the ERK pathway

BackgroundTooth agenesis, one of the most common developmental anomalies, can affect the function and esthetics of patients. The aim of the present study was to identify genetic clues for familial tooth agenesis and explore the underlying mechanisms, focusing on the role of human dental pulp stem cells (hDPSCs).MethodsWe applied Sanger sequencing to identify the cause of oligodontia in a Chinese family. DNA transfection and functional analysis in DPSCs was also performed to explore the impact of the identified mutation on this phenotype.ResultsIn this study, a novel frameshift mutation, the twenty-nucleotide deletion (c.128_147del20, p.Met43Serfsx125), in exon1 of MSX1 was detected in a Chinese family causing autosomal dominant nonsyndromic oligodontia. The mutation cosegregated with the tooth agenesis phenotype in this family. DPSCs transfected with mutant MSX1 plasmid showed decreased capacity of osteo/odontogenic differentiation with a lower expression level of dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) compared with those transfected with control MSX1 plasmid. Mechanically, control MSX1 showed nuclear localization while the mutant MSX1 inhibited its nuclear translocation and localized on the cytoplasm to inhibit ERK phosphorylation. Furthermore, we inhibited the ERK pathway using ERK inhibitor (U0126) treatment in control MSX1-transfected DPSCs which could downregulate mineralized nodule formation and the expression of odontogenic genes.ConclusionWe demonstrated a novel MSX1 mutation causing familial nonsyndromic oligodontia and mechanically MSX1 regulates odontogenesis through the ERK signaling pathway in human dental pulp stem cells.