The Experts below are selected from a list of 1356 Experts worldwide ranked by ideXlab platform
Dong Han - One of the best experts on this subject based on the ideXlab platform.
-
novel msx1 variants identified in families with nonsyndromic Oligodontia
International Journal of Oral Science, 2021Co-Authors: Jinglei Zheng, Hailan Feng, Haochen Liu, Tao Cai, Yang Liu, Dong HanAbstract: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.
-
Functional study of novel PAX9 variants: the paired domain and non-syndromic Oligodontia.
Oral Diseases, 2020Co-Authors: Kai Sun, Hailan Feng, Haochen Liu, Tao Cai, Yang Liu, I-ting Yeh, Liutao Zhang, Dong HanAbstract:OBJECTIVES To investigate pathogenic variants of the paired box 9 (PAX9) gene in patients with non-syndromic Oligodontia, and the functional impact of these variants. SUBJECTS AND METHODS Whole exome sequencing and Sanger sequencing were utilised 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. RESULTS 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 localisations of frameshift variants, and luciferase assay showed impaired downstream transactivation activities of the bone morphogenetic protein 4 (BMP4) gene in all variants. CONCLUSIONS 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
Human Mutation, 2020Co-Authors: L W Zhang, Hailan Feng, Sing-wai Wong, Haochen Liu, Tao Cai, Yang Liu, Zhuangzhuang Fan, Jinglei Zheng, Yongsheng Zhou, Dong HanAbstract: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.
-
Involvement of and Interaction between WNT10A and EDA Mutations in Tooth Agenesis Cases in the Chinese Population
2016Co-Authors: Dong Han, Shujuan Song, Hailan Feng, Baojing Bai, Zhenting ZhangAbstract:Background: Dental agenesis is the most common, often heritable, developmental anomaly in humans. Although WNT10A gene mutations are known to cause rare syndromes associated with tooth agenesis, including onycho-odontodermal dysplasia (OODD), Schöpf-Schulz-Passarge syndrome (SSPS), hypohidrotic ectodermal dysplasia (HED), and more than half of the cases of isolated Oligodontia recently, the genotype-phenotype correlations and the mode of inheritance of WNT10A mutations remain unclear. The phenotypic expression with WNT10A mutations shows a high degree of variability, suggesting that other genes might function with WNT10A in regulating ectodermal organ development. Moreover, the involvement of mutations in other genes, such as EDA, which is also associated with HED and isolated tooth agenesis, is not clear. Therefore, we hypothesized that EDA mutations interact with WNT10A mutations to play a role in tooth agenesis. Additionally, EDA, EDAR, and EDARADD encode signaling molecules in the Eda/Edar/NF-kB signaling pathways, we also checked EDAR and EDARADD in this study. Methods: WNT10A, EDA, EDAR and EDARADD were sequenced in 88 patients with isolated Oligodontia and 26 patients with syndromic tooth agenesis. The structure of two mutated WNT10A and two mutated EDA proteins was analyzed. Results: Digenic mutations of both WNT10A and EDA were identified in 2 of 88 (2.27%) isolated Oligodontia cases and 4 of 26 (15.38%) syndromic tooth agenesis cases. No mutation in EDAR or EDARADD gene was found
-
mutations in wnt10b are identified in individuals with Oligodontia
American Journal of Human Genetics, 2016Co-Authors: Wenli Yang, Dong Han, Xiao Xia Zhang, Sing-wai Wong, Baojing Bai, Xi Wang, Sen Guo, Yao Liu, Zhong Sheng SunAbstract:Tooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom Oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic Oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262∗], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with Oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells.
Hailan Feng - One of the best experts on this subject based on the ideXlab platform.
-
novel msx1 variants identified in families with nonsyndromic Oligodontia
International Journal of Oral Science, 2021Co-Authors: Jinglei Zheng, Hailan Feng, Haochen Liu, Tao Cai, Yang Liu, Dong HanAbstract: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.
-
Functional study of novel PAX9 variants: the paired domain and non-syndromic Oligodontia.
Oral Diseases, 2020Co-Authors: Kai Sun, Hailan Feng, Haochen Liu, Tao Cai, Yang Liu, I-ting Yeh, Liutao Zhang, Dong HanAbstract:OBJECTIVES To investigate pathogenic variants of the paired box 9 (PAX9) gene in patients with non-syndromic Oligodontia, and the functional impact of these variants. SUBJECTS AND METHODS Whole exome sequencing and Sanger sequencing were utilised 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. RESULTS 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 localisations of frameshift variants, and luciferase assay showed impaired downstream transactivation activities of the bone morphogenetic protein 4 (BMP4) gene in all variants. CONCLUSIONS 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
Human Mutation, 2020Co-Authors: L W Zhang, Hailan Feng, Sing-wai Wong, Haochen Liu, Tao Cai, Yang Liu, Zhuangzhuang Fan, Jinglei Zheng, Yongsheng Zhou, Dong HanAbstract: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.
-
Involvement of and Interaction between WNT10A and EDA Mutations in Tooth Agenesis Cases in the Chinese Population
2016Co-Authors: Dong Han, Shujuan Song, Hailan Feng, Baojing Bai, Zhenting ZhangAbstract:Background: Dental agenesis is the most common, often heritable, developmental anomaly in humans. Although WNT10A gene mutations are known to cause rare syndromes associated with tooth agenesis, including onycho-odontodermal dysplasia (OODD), Schöpf-Schulz-Passarge syndrome (SSPS), hypohidrotic ectodermal dysplasia (HED), and more than half of the cases of isolated Oligodontia recently, the genotype-phenotype correlations and the mode of inheritance of WNT10A mutations remain unclear. The phenotypic expression with WNT10A mutations shows a high degree of variability, suggesting that other genes might function with WNT10A in regulating ectodermal organ development. Moreover, the involvement of mutations in other genes, such as EDA, which is also associated with HED and isolated tooth agenesis, is not clear. Therefore, we hypothesized that EDA mutations interact with WNT10A mutations to play a role in tooth agenesis. Additionally, EDA, EDAR, and EDARADD encode signaling molecules in the Eda/Edar/NF-kB signaling pathways, we also checked EDAR and EDARADD in this study. Methods: WNT10A, EDA, EDAR and EDARADD were sequenced in 88 patients with isolated Oligodontia and 26 patients with syndromic tooth agenesis. The structure of two mutated WNT10A and two mutated EDA proteins was analyzed. Results: Digenic mutations of both WNT10A and EDA were identified in 2 of 88 (2.27%) isolated Oligodontia cases and 4 of 26 (15.38%) syndromic tooth agenesis cases. No mutation in EDAR or EDARADD gene was found
-
a novel axin2 missense mutation is associated with non syndromic Oligodontia
PLOS ONE, 2015Co-Authors: Haochen Liu, Tingting Ding, Yuan Zhan, Hailan FengAbstract:Oligodontia is defined as the congenital absence of six or more permanent teeth, excluding the third molars. Oligodontia may contribute to masticatory dysfunction, speech alteration, aesthetic problems and malocclusion. Numerous gene mutations have been association with Oligodontia. In the present study, we identified a de novo AXIN2 missense mutation (c.314T>G) in a Chinese individual with non-syndromic Oligodontia. This mutation results in the substitution of Val at residue 105 for Gly (p.Val105Gly); residue 105 is located in the highly conserved regulator of G protein signaling (RGS) domain of the AXIN2 protein. This is the first report indicating that a mutation in the RGS domain of AXIN2 is responsible for non-syndromic Oligodontia. Our study supports the relationship between AXIN2 mutation and non-syndromic Oligodontia and extends the mutation spectrum of the AXIN2 gene.
Pekka Nieminen - One of the best experts on this subject based on the ideXlab platform.
-
familial Oligodontia and regional odontodysplasia associated with a pax9 initiation codon mutation
Clinical Oral Investigations, 2019Co-Authors: Sari Koskinen, Pekka Nieminen, Riikka Keskifilppula, Heikki Alapulli, Vuokko AnttonenAbstract:Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas Oligodontia refers to the absence of at least six teeth, excluding the third molars. Mutations in several genes including MSX1, PAX9, AXIN2, and WNT10A have been shown to cause non-syndromic tooth agenesis. Regional odontodysplasia (RO), also known as “ghost teeth,” is a rare developmental anomaly of tooth formation affecting both dentitions. Some possible causes of RO have been suggested, yet the etiology remains unknown. Because the phenotypes of both Oligodontia and RO co-occur in one Finnish family, the aim here was to investigate the genetic etiology of the two conditions. A mutation screening of the genes MSX1, PAX9, AXIN2, and WNT10A was performed for the family members of a RO patient and family history of Oligodontia. An initiation codon mutation of the PAX9 gene was found in the proband and segregating with Oligodontia in the family. The etiology of regional odontodysplasia (RO) may be genetic and the same genes can be involved both in RO and tooth agenesis. Our results give new insights into the etiology of regional odontodysplasia, yet further results are needed.
-
Familial Oligodontia and regional odontodysplasia associated with a PAX9 initiation codon mutation.
Clinical Oral Investigations, 2019Co-Authors: Sari Koskinen, Pekka Nieminen, Heikki Alapulli, Riikka Keski-filppula, Vuokko AnttonenAbstract:Objective Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas Oligodontia refers to the absence of at least six teeth, excluding the third molars. Mutations in several genes including MSX1, PAX9, AXIN2, and WNT10A have been shown to cause non-syndromic tooth agenesis. Regional odontodysplasia (RO), also known as "ghost teeth," is a rare developmental anomaly of tooth formation affecting both dentitions. Some possible causes of RO have been suggested, yet the etiology remains unknown. Because the phenotypes of both Oligodontia and RO co-occur in one Finnish family, the aim here was to investigate the genetic etiology of the two conditions. Materials and methods A mutation screening of the genes MSX1, PAX9, AXIN2, and WNT10A was performed for the family members of a RO patient and family history of Oligodontia. Results An initiation codon mutation of the PAX9 gene was found in the proband and segregating with Oligodontia in the family. Conclusions The etiology of regional odontodysplasia (RO) may be genetic and the same genes can be involved both in RO and tooth agenesis. Clinical relevance Our results give new insights into the etiology of regional odontodysplasia, yet further results are needed.
-
investigating the etiology of multiple tooth agenesis in three sisters with severe Oligodontia
Orthodontics & Craniofacial Research, 2008Co-Authors: S Swinnen, Sirpa Arte, Pekka Nieminen, Koenraad Devriendt, Isabelle Bailleulforestier, Carine CarelsAbstract:Structured Abstract Authors – Swinnen S, Bailleul-Forestier I, Arte S, Nieminen P, Devriendt K, Carels C Objectives – To describe the dentofacial phenotypes of three sisters with severe non-syndromic Oligodontia, to report on the mutation analysis in three genes, previously shown to cause various phenotypes of non-syndromic Oligodontia and in two other suspected genes. Based on the phenotypes in the pedigree of this family, the different possible patterns of transmission are discussed. Methods – Anamnestic data and a panoramic radiograph were taken to study the phenotype of the three sisters and their first-degree relatives. Blood samples were also taken to obtain their karyotypes and DNA samples. Mutational screening was performed for the MSX1, PAX9, AXIN2, DLX1 and DLX2 genes. Results – The probands’ pedigree showed evidence for a recessive or multifactorial inheritance pattern. Normal chromosomal karyotypes were found and – despite the severe Oligodontia present in all three sisters – no mutation appeared to be present in the five genes studied so far in these patients. Conclusions – In the three sisters reported, their common Oligodontia phenotype is not caused by mutations in the coding regions of MSX1, PAX9, AXIN2, DLX1 or DLX2 genes, but genetic factors most probably play a role as all three sisters were affected. Environmental and epigenetic factors as well as genes regulating odontogenesis need further in vivo and in vitro investigation to explain the phenotypic heterogeneity and to increase our understanding of the odontogenic processes.
-
identification of a novel mutation in the pax9 gene in a family affected by Oligodontia and other dental anomalies
European Journal of Oral Sciences, 2007Co-Authors: Victoria Tallonwalton, Sirpa Arte, Pekka Nieminen, Maria Cristina Manzanarescespedes, Patricia Carvalholobato, Ivan Valdiviagandur, Antonio Garciasusperregui, Francesc VenturaAbstract:The objective of the present work was to study the phenotype and the genotype of three generations of a family affected by Oligodontia and other dental anomalies. These family members also presented systemic conditions such as hypercholesterolemia, hypothyroidism, diabetes mellitus, scoliosis, and congenital cardiovascular anomalies. Clinical evaluation, panoramic radiographs, and anamnestic data were used for dental analysis. DNA extraction was carried out from gum samples or buccal swabs. A mutation was identified in six subjects across three generations affected by Oligodontia, as well as different phenotypical manifestations, both systemic and oral. The previously undescribed PAX9 mutation was observed in the paired box (exon 2); this was a heterozygote transition of C175 to T, implying the change of arginine 59 for a termination codon. These results strongly suggested that the identified mutation was the etiological cause of the Oligodontia. However, in two family members affected by both hypodontia and peg-shaped upper lateral incisors, no mutations in the PAX9 and MSX1 genes were identified. This fact underscores the importance that other presently unknown genes and developmental factors have in tooth development and in the etiology of dental anomalies.
-
Exclusion of coding region mutations in MSX1, PAX9 and AXIN2 in eight patients with severe Oligodontia phenotype.
Orthodontics and Craniofacial Research, 2006Co-Authors: A Gerits, Pekka Nieminen, S. De Muynck, Carine CarelsAbstract:Structured Abstract Authors – Gerits A, Nieminen P, De Muynck S, Carels C Purpose – This paper describes the screening of eight patients with severe Oligodontia for PAX9 and AXIN2 mutations. Subjects and Methods – Anamnestic data and a panoramic radiograph were collected to study the phenotype of eight patients with Oligodontia and their first-degree relatives. A blood sample was taken for a mutational screening for PAX9 and AXIN2 mutations. Results – No mutations were discovered, but a unique nucleotide change in a conserved 5′ flanking region of PAX9 was revealed. Earlier screening of the same patients for MSX1 mutations also had a negative outcome. Conclusions – Considering the discrepancy between the high incidence rate of agenesis and the relatively small number of reported causative mutations in PAX9, MSX1 and AXIN2 genes, the genetic contribution to Oligodontia probably is much more heterogeneous than expected so far. Therefore negative results, like the present exclusion data, should be published more often in order to get a better appreciation of the relative contribution of these specific mutations causing Oligodontia. In this context the exact number of tested probands also should be mentioned at all cases. Recent evidence of PAX9–MSX1 protein interactions in odontogenesis as well as other genes and developmental factors should receive more attention.
Anita Visser - One of the best experts on this subject based on the ideXlab platform.
-
oral health related quality of life in dutch children diagnosed with Oligodontia a cross sectional study
International Journal of Environmental Research and Public Health, 2019Co-Authors: Marieke A P Filius, Marijn Créton, Marco S. Cune, Arjan Vissink, Gerry M. Raghoebar, Anita VisserAbstract:There is need to get insight into condition-specific oral health-related quality of life in Dutch children with Oligodontia. Between October 2014 and March 2017, 11-17-year-old Oligodontia patients were approached to join a study assessing the impact of Oligodontia on condition-specific oral health-related quality of life (OHrQoL). The patients received a condition-specific OHrQoL questionnaire prior to the start of orthodontic treatment. Non-Oligodontia children in the same age group, but also requiring orthodontic treatment, were approached to serve as a control. The Fisher's Exact Test was used for comparison purposes with the control group because of the small group sizes. Furthermore, subgroup analyses were performed for gender, age, number of congenitally missing teeth, tooth agenesis in the aesthetic region, orthodontic classification and microdontia via independent t-tests. p-values of <0.05 were considered statistically significant. Twenty-eight Oligodontia patients and 23 controls agreed to participate. The Oligodontia patients' scores were comparable to the controls except for the items about dental appearance and treatment complexity. The impact of Oligodontia on OHrQoL in youngsters is limited and mainly concerns dental appearance and the complexity of the treatment.
-
long term implant performance and patients satisfaction in Oligodontia
Journal of Dentistry, 2018Co-Authors: Marieke A P Filius, Marco S. Cune, Arjan Vissink, Gerry M. Raghoebar, Anita VisserAbstract:Abstract Objectives To assess long-term (≥10 years) implant survival, peri-implant health, patients’ satisfaction and oral health related quality of life (OHQoL) in Oligodontia patients rehabilitated with implant-based fixed prosthodontics. Methods All Oligodontia patients treated ≥10 years previously with implant-based fixed prosthodontics at the University Medical Center Groningen, The Netherlands, were approached to participate. Clinical (plaque index, bleeding index, pocket probing depth) and radiographic (marginal bone level) data were collected between February and May 2016. Surgical implant details (e.g., bone augmentation) and implant loss were recalled from the medical records. Patients completed a satisfaction questionnaire (maximum score 10, high score favourable satisfaction) and the Oral Health Impact Profile (OHIP-NL49, maximum score 196, low score favourable satisfaction) to rate OHQoL. Implant survival was expressed according to Kaplan Meier. The Mann-Whitney U Test was used for the other analyses. Results Forty-one patients had been treated with implant-based fixed prosthodontics (n = 258) ≥10 years previously. Cumulative 10-year implant survival of these 41 patients was 89.1% (95%CI 85.2–93.0%). Twenty-eight of them (n = 163 implants) were willing to visit us for additional clinical and radiographic assessments. In these 28 patients, highest peri-implant bone loss was observed for implants placed in augmented bone (p 10). Conclusions Long-term survival, satisfaction and OHQoL results reveal that implant treatment is a predictable and satisfactory treatment modality for Oligodontia, although peri-implant mucositis and peri-implantitis are common. Clinical significance This study showed unique long-term (≥10 years) results about implant survival, peri-implant health, patients’ satisfaction and OHQoL in Oligodontia patients rehabilitated with implant-based fixed prosthodontics.
-
Three-dimensional computer-guided implant placement in Oligodontia.
International journal of implant dentistry, 2017Co-Authors: Marieke A P Filius, Joep Kraeima, Arjan Vissink, Krista I. Janssen, Gerry M. Raghoebar, Anita VisserAbstract:The aim of computer-designed surgical templates is to attain higher precision and accuracy of implant placement, particularly for compromised cases. The purpose of this study is to show the benefit of a full three-dimensional virtual workflow to guide implant placement in Oligodontia cases where treatment is challenging due compromised bone quantity and limited interdental spaces. A full, digitalized workflow was performed for implant placement in two Oligodontia patients. Accuracy was assessed by calculating the coordinates of the entry point (shoulder) and apex (tip) as well as the angular deviation of the planned and actual implants. Implant placement could be well performed with the developed computer-designed templates in Oligodontia. Mean shoulder deviation was 1.41 mm (SD 0.55), mean apical deviation was 1.20 mm (SD 0.54) and mean angular deviation was 5.27° (SD 2.51). Application of computer-designed surgical templates, as described in this technical advanced article, aid in predictable implant placement in Oligodontia where bone quantity is scarce and interdental spaces are limited.
Haochen Liu - One of the best experts on this subject based on the ideXlab platform.
-
novel msx1 variants identified in families with nonsyndromic Oligodontia
International Journal of Oral Science, 2021Co-Authors: Jinglei Zheng, Hailan Feng, Haochen Liu, Tao Cai, Yang Liu, Dong HanAbstract: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.
-
Functional study of novel PAX9 variants: the paired domain and non-syndromic Oligodontia.
Oral Diseases, 2020Co-Authors: Kai Sun, Hailan Feng, Haochen Liu, Tao Cai, Yang Liu, I-ting Yeh, Liutao Zhang, Dong HanAbstract:OBJECTIVES To investigate pathogenic variants of the paired box 9 (PAX9) gene in patients with non-syndromic Oligodontia, and the functional impact of these variants. SUBJECTS AND METHODS Whole exome sequencing and Sanger sequencing were utilised 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. RESULTS 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 localisations of frameshift variants, and luciferase assay showed impaired downstream transactivation activities of the bone morphogenetic protein 4 (BMP4) gene in all variants. CONCLUSIONS 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
Human Mutation, 2020Co-Authors: L W Zhang, Hailan Feng, Sing-wai Wong, Haochen Liu, Tao Cai, Yang Liu, Zhuangzhuang Fan, Jinglei Zheng, Yongsheng Zhou, Dong HanAbstract: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.
-
a novel axin2 missense mutation is associated with non syndromic Oligodontia
PLOS ONE, 2015Co-Authors: Haochen Liu, Tingting Ding, Yuan Zhan, Hailan FengAbstract:Oligodontia is defined as the congenital absence of six or more permanent teeth, excluding the third molars. Oligodontia may contribute to masticatory dysfunction, speech alteration, aesthetic problems and malocclusion. Numerous gene mutations have been association with Oligodontia. In the present study, we identified a de novo AXIN2 missense mutation (c.314T>G) in a Chinese individual with non-syndromic Oligodontia. This mutation results in the substitution of Val at residue 105 for Gly (p.Val105Gly); residue 105 is located in the highly conserved regulator of G protein signaling (RGS) domain of the AXIN2 protein. This is the first report indicating that a mutation in the RGS domain of AXIN2 is responsible for non-syndromic Oligodontia. Our study supports the relationship between AXIN2 mutation and non-syndromic Oligodontia and extends the mutation spectrum of the AXIN2 gene.
-
a novel non stop mutation in msx1 causing autosomal dominant non syndromic Oligodontia
Mutagenesis, 2014Co-Authors: Sing-wai Wong, Dong Han, Haochen Liu, Huaiguang Chang, Hongshan Zhao, Yixiang Wang, Hailan FengAbstract:Oligodontia, which is the congenital absence of six or more permanent teeth, excluding the third molars, may contribute to masticatory dysfunction, speech alteration, aesthetic problems and malocclusion. Msh homeobox 1 (MSX1) was the first gene identified as causing non-syndromic Oligodontia. In this study, we identified a novel heterozygous non-stop mutation (c.910_911dupTA, p.*304Tyrext*48) in MSX1 in a Chinese family with autosomal dominant non-syndromic Oligodontia. This novel mutation substitutes the stop codon with a tyrosine residue, potentially adding 48 amino acids to the C-terminus of MSX1. Further in vitro study found that mutant MSX1 could be expressed but had lost its ability to enter the nucleus. This is the first report indicating that a non-stop mutation in MSX1 is responsible for Oligodontia. This study broadens the mutation spectrum for MSX1 and provides a new way to clarify the mechanism of MSX1 in tooth agenesis.
