The Gene Network Underlying Hypodontia

Yin, Wei; Bian, Zhuan

doi:10.1177/0022034515583999

Cited by 99 publications

(135 citation statements)

References 58 publications

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“…Previous studies have mainly focused on tooth agenesis, associating the MSX1 variants to the type and number of missing teeth, and it is generally concluded that the most frequently missing teeth in case of MSX1 variants are the second premolars. [13][14][15] In a previous study we identified a novel MSX1 mutation causing tooth agenesis with cleft lip, further confirming that different MSX1 mutations may cause different phenotypes. 16 This review reveals a strong correlation between observed phenotypes and the location in the MSX1 protein structure of the disease causing mutations.…”

Section: Introductionsupporting

confidence: 56%

MSX1 mutations and associated disease phenotypes: genotype-phenotype relations

Liang

Hoff

Lange³

et al. 2016

Eur J Hum Genet

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The Msx1 transcription factor is involved in multiple epithelial-mesenchymal interactions during vertebrate embryogenesis. It has pleiotropic effects in several tissues. In humans, MSX1 variants have been related to tooth agenesis, orofacial clefting, and nail dysplasia. We correlate all MSX1 disease causing variants to phenotypic features to shed light on this hitherto unclear association. MSX1 truncations cause more severe phenotypes than in-frame variants. Mutations in the homeodomain always cause tooth agenesis with or without other phenotypes while mutations outside the homeodomain are mostly associated with non-syndromic orofacial clefts. Downstream effects can be further explored by the edgetic perturbation model. This information provides new insights for genetic diagnosis and for further functional analysis of MSX1 variants.

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Section: Introductionsupporting

confidence: 56%

MSX1 mutations and associated disease phenotypes: genotype-phenotype relations

Liang

Hoff

Lange³

et al. 2016

Eur J Hum Genet

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“…individuals with hypodontia were mandibular second premolars, followed by maxillary lateral incisors, as reported in a recent meta-analysis, 33 it is likely that there is an overlapping phenotype in some of the individuals with WNT10A and WNT10B mutations. The selective pattern in WNT10B mutants is also different from that of mutations in other oligodontia-associated genes, such as MSX1 (missing second premolar) and PAX9 (agenesis of molars), as described previously 7,10,11,34 and currently in the individuals with the p.Ile97Leufs*217 variant ( Figure S1). Regardless, protein-protein-interaction and genetic studies have shown crosstalk between PAX9 and the Wnt pathway (e.g., AXIN2) or MSX1 in dental tissues, 11 which are essential for the establishment of the odontogenic potential of the mesenchyme.…”

mentioning

confidence: 68%

“…The selective pattern in WNT10B mutants is also different from that of mutations in other oligodontia-associated genes, such as MSX1 (missing second premolar) and PAX9 (agenesis of molars), as described previously 7,10,11,34 and currently in the individuals with the p.Ile97Leufs*217 variant ( Figure S1). Regardless, protein-protein-interaction and genetic studies have shown crosstalk between PAX9 and the Wnt pathway (e.g., AXIN2) or MSX1 in dental tissues, 11 which are essential for the establishment of the odontogenic potential of the mesenchyme. However, the underlying mechanism of different genotype-phenotype correlations observed here remains elusive.…”

mentioning

confidence: 68%

“…Presumably, additional crucial components in several defined canonical pathways (such as BMP, FGF, NF-kB, P53, PAX, and Wnt, which involve tooth development) could be the candidates. 11 In the present study, we applied wholeexome sequencing (WES) and Sanger sequencing to identify potential genetic defects in a large cohort of individuals with oligodontia. We also explored the potential effects of the identified mutations on cellular differentiation of dental pulp stem cells (DPSCs).…”

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confidence: 99%

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Mutations in WNT10B Are Identified in Individuals with Oligodontia

Yü

Yang

Han

et al. 2016

The American Journal of Human Genetics

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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.

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“…Our understanding of the genetics underlying tooth agenesis has progressed greatly in recent years, with approximately 80 genes found to be related to tooth agenesis [3]. However, OMIM lists 111 different syndromes associated with oligodontia.…”

Section: Introductionmentioning

confidence: 99%

Associations between ectodermal dysplasia, psychological distress and quality of life in a group of adults with oligodontia

Saltnes

Jensen

Saeves

et al. 2017

Acta Odontologica Scandinavica

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Objective: The aim of this study was to assess demographics, self-reported signs of ectodermal dysplasia (problems with hair, nails, skin and sweat glands), present teeth, previous dental treatment, psychological distress and QoL in individuals with oligodontia, and to explore the associations between these factors. We also aimed to compare the level of psychological distress and QoL between the study group and normative samples. Methods: Forty-seven individuals with oligodontia registered at a resource centre in Norway were included in the study. The participants completed self-administered questionnaires on demographics, ED signs, dental treatments, psychological distress and QoL (overall, health-related-and oral healthrelated QoL). Relevant statistics (independent t-test, correlation analysis and hierarchical multiple regressions) were used. Results: Thirty-five participants reported ED signs. Forty-one participants had tooth replacements (nine had removable dentures). Sixteen had 10 present teeth, 13 perceived dry mouth and seven were unemployed. Persons with 10 present teeth had higher anxiety-and depression-scores than those having >10 present teeth. Unemployment, dry mouth and removable dentures indicated poor healthrelated-and oral health related QoL. Compared to a normative sample; the study group had significantly poorer mental health (MH)-related QoL, mean (SD); (51.1(8.2) versus 46.8(9.3), p < .001) and more anxiety, mean (SD); (4.5(3.1) versus 6.7(3.6), p < .001). ED signs and treatments were most important for psychological distress and MH related QoL (MCS), whereas demographic parameters were most important for the other QoL measures. Conclusions: The psychological burden of oligodontia is significant, emphasizing the importance of a holistic approach by caregivers. ARTICLE HISTORY

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The Gene Network Underlying Hypodontia

Cited by 99 publications

References 58 publications

MSX1 mutations and associated disease phenotypes: genotype-phenotype relations

MSX1 mutations and associated disease phenotypes: genotype-phenotype relations

Mutations in WNT10B Are Identified in Individuals with Oligodontia

Associations between ectodermal dysplasia, psychological distress and quality of life in a group of adults with oligodontia

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