Study of rs12532, rs8670 Polymorphism of Msh Homeobox 1 (MSX1), rs61754301, rs4904155 Polymorphism of Paired Box Gene 9 (PAX9), and rs2240308 Polymorphism of Axis Inhibitor Protein 2 (AXIN2) Genes in Nonsyndromic Hypodontia

Martha, Krisztina; Kerekes-Máthé, Bernadette; Moldovan, Valeriu; Bănescu, Claudia

doi:10.1155/2019/2183720

Cited by 6 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to the latest published data, our study is the first one who analyzed the AXIN2 rs2240308 variant on CHDs patients. Previous studies evaluated the mentioned variant on patients with hypodontia and demonstrated that the presence of a variant allele was associated with frontal agenesis [29]. Also, the mentioned variant was previously associated with cancer risk, such as colorectal cancer [30], breast cancer [31], and Hirschsprung disease [32].…”

Section: Discussionmentioning

confidence: 99%

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

Crauciuc

Iancu

Olah

et al. 2020

IJERPH

Self Cite

View full text Add to dashboard Cite

This study aimed to investigate possible associations of the susceptibility to congenital heart defects (CHDs) with AXIN1 rs1805105, rs12921862 and rs370681 gene variants and haplotypes, and AXIN2 rs2240308 gene variant. Significant associations were identified for AXIN1 rs370681 and AXIN2 rs2240308 variants. AXIN1 rs370681 variant was significantly associated with decreased odds of CHDs (adjusted OR varying from 0.13 to 0.28 in codominant, dominant and recessive gene models), while the AXIN2 rs2240308 variant was associated with increased odds of CHD in the dominant model. The haplotype-based generalized linear model regression of AXIN1 rs1805105, rs12921862 and rs370681 variants revealed that C-C-C and C-C-T haplotypes significantly increased the risk of CHDs (p < 0.05). No significant second order epistatic interactions were found between investigated variants (AXIN1 rs1805105, rs12921862, rs370681, and AXIN2 rs2240308). Our conclusion is that AXIN1 rs1805105, rs12921862, and rs370681 (C-C-C and C-C-T) haplotypes and AXIN2 rs2240308 contribute to CHDs susceptibility.

show abstract

Section: Discussionmentioning

confidence: 99%

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

Crauciuc

Iancu

Olah

et al. 2020

IJERPH

Self Cite

View full text Add to dashboard Cite

show abstract

“…Based on the number of missing teeth (not including third molars), tooth agenesis can be classified as hypodontia (less than 6 missing teeth), oligodontia (6 or more missing teeth), and anodontia (all teeth missing) [ 3 , 4 ]. To date, NSH has been reported to be associated with mutations in ectodysplasin-A ( EDA ), ectodysplasin-A receptor ( EDAR ), EDAR-associated death domain ( EDARADD ), wnt family member 10A ( WNT10A ), wnt family member 10B ( WNT10B ), paired box 9 ( PAX9 ), msh homeobox 1 ( MSX1 ), axis inhibition protein 2 ( AXIN2 ), and inhibitor of nuclear factor kappa B kinase regulatory subunit gamma ( IKBKG ) [ 5 – 7 ]. Among these, EDA mutations could cause SH, which appears as an X-linked hypohidrotic ectodermal dysplasia (XLHED) clinical feature, and they have also been linked to isolated tooth agenesis, most likely due to complete or partial disruption of the EDA signalling pathway [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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

Pan

Lü

Peng

et al. 2021

Stem Cells International

View full text Add to dashboard Cite

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.

show abstract

“…According to the number of missing teeth (not including third molars), tooth agenesis can be classi ed as hypodontia (less than 6 missing teeth), oligodontia (6 or more than 6 missing teeth), and anodontia (all teeth missing) [4][5]. To date NSH has been reported to be associated with mutations in ectodysplasin-A (EDA), ectodysplasin-A receptor (EDAR), EDAR associated death domain (EDARADD), wnt family member 10A (WNT10A), wnt family member 10B (WNT10B), paired box 9 (PAX9), msh homeobox 1 (MSX1), axis inhibition protein 2 (AXIN2) and inhibitor of nuclear factor kappa B kinase regulatory subunit gamma (IKBKG) [6][7]. Among which, EDA mutations could cause SH, which appears as a clinical feature of X-linked hypohidrotic ectodermal dysplasia (XLHED), and also have been linked to isolated tooth agenesis, most likely due to complete or partial disruption of the EDA signaling pathway [8][9].…”

Section: Introductionmentioning

confidence: 99%

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

Pan

Peng

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundMutations of the Ectodysplasin-A (EDA) gene are generally associated with other developmental anomalies (syndrome hypohidrotic ectodermal dysplasia) or as an isolated condition (non-syndromic tooth agenesis). The influence of EDA mutations on dentinogenesis and odontoblast differentiation have not been reported. The aim of the present study was to identify genetic clues for familial nonsyndromic oligodontia and explore the underlying mechanisms, focusing on the role of human dental pulp stem cells (hDPSCs).MethodsThe candidate genes sequences were performed by PCR amplification and Sanger sequencing. Functional analysis and pathogenesis associated with EDA mutations in hDPSCs were also investigated to explore the impact of the identified mutation on this phenotype. Capillary electrophoresis (CE) was used to detect X chromosome inactivation (XCI) on the blood of female carrier.ResultsIn this study, we identified a reported EDA mutation in a Chinese family：a missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with those transfected with control EDA lentivirus. Mechanically, the mutant EDA inhibited the activation of the NF-κB pathway. The results of CE showed that symptomatic female carrier had a skewed XCI with a preferential inactivation of the X chromosome carrying the normal allele.ConclusionIn summary, we demonstrated EDA mutation result in non-syndromic tooth agenesis in heterozygous females and mechanically EDA regulates odontogenesis through the NF-κB signaling pathway in human dental pulp stem cells.

show abstract

Study of rs12532, rs8670 Polymorphism of Msh Homeobox 1 (MSX1), rs61754301, rs4904155 Polymorphism of Paired Box Gene 9 (PAX9), and rs2240308 Polymorphism of Axis Inhibitor Protein 2 (AXIN2) Genes in Nonsyndromic Hypodontia

Cited by 6 publications

References 23 publications

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

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

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

Contact Info

Product

Resources

About