Dataset Information

Screening PAX9, MSX1 and WNT10A Mutations in 4 Iranian Families with Non-Syndromic Tooth Agenesis.

ABSTRACT: Background:Tooth agenesis is one of the most common developmental anomalies in human and the main reasons for its occurrence are still unknown. Mutations of several genes such as PAX9, MSX1, AXIN2, KDF1 and WNT10A have been reported which are associated with non-syndromic tooth agenesis. However, PAX9, MSX1 and WNT10A are commonly reported in the literature. Hence, the aim of this study was to investigate the mutations of these genes in 4 Iranian families with non-syndromic tooth agenesis. Methods:DNA extractions from peripheral blood cells of patients with non-syndromic tooth agenesis from 4 unrelated Iranian families were performed by salting out method, and the candidate genes were amplified then followed by Sanger sequencing method. Results:One missense variant (rs4904210) and 4 Single Nucleotide Polymorphisms (SNPs) (rs2236007, rs12883298, rs12882923 and rs12883049) were found in PAX9 gene. Five variants (rs149370601, rs8670, rs186861426 and rs774949973) including a missense variant (rs36059701) were detected in MSX1 gene and no variants were found in WNT10A gene. Conclusion:All variants were analyzed based on bioinformatics websites and Iranian gene databases, and as a result, it was revealed that variants of PAX9, MSX1 and WNT10A may not play a role in non-syndromic tooth agenesis among Iranian cases.

SUBMITTER: Safari S

PROVIDER: S-EPMC7502159 | biostudies-literature | 2020 Oct-Dec

REPOSITORIES: biostudies-literature

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Publications

Screening PAX9, MSX1 and WNT10A Mutations in 4 Iranian Families with Non-Syndromic Tooth Agenesis.

Safari Shiva S Ebadifar Asghar A Najmabadi Hossien H Kamali Koorosh K Abedini Seyedeh Sedigheh SS

Avicenna journal of medical biotechnology 20201001 4

<h4>Background</h4>Tooth agenesis is one of the most common developmental anomalies in human and the main reasons for its occurrence are still unknown. Mutations of several genes such as PAX9, MSX1, AXIN2, KDF1 and WNT10A have been reported which are associated with non-syndromic tooth agenesis. However, PAX9, MSX1 and WNT10A are commonly reported in the literature. Hence, the aim of this study was to investigate the mutations of these gene ...[more]

PMID: 33014315

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Project description:Since MSX1 and PAX9 are linked to the pathogenesis of nonsyndromic tooth agenesis, we performed detailed mutational analysis of these two genes sampled from Japanese patients. We identified two novel MSX1 variants with an amino acid substitution within the homeodomain; Thr174Ile (T174I) from a sporadic hypodontia case and Leu205Arg (L205R) from a familial oligodontia case. Both the Thr174 and Leu205 residues in the MSX1 homeodomain are highly conserved among different species. To define possible roles of mutations at these amino acids in the pathogenesis of nonsyndromic tooth agenesis, we performed several functional analyses. It has been demonstrated that MSX1 plays a pivotal role in hard tissue development as a suppressor for mesenchymal cell differentiation. To evaluate the suppression activity of the variants in mesenchymal cells, we used the myoD-promoter, which is one of convenient reporter assay system for MSX1. Although the gene products of these MSX1 variants are stable and capable of normal nuclear localization, they do not suppress myoD-promoter activity in differentiated C2C12 cells. To clarify the molecular mechanisms underlying our results, we performed further analyses including electrophoretic mobility shift assays, and co-immunoprecipitation assays to survey the molecular interactions between the mutant MSX1 proteins and the oligonucleotide DNA with MSX1 consensus binding motif or EZH2 methyltransferase. Since EZH2 is reported to interact with MSX1 and regulate MSX1 mediated gene suppression, we hypothesized that the T174I and L205R substitutions would impair this interaction. We conclude from the results of our experiments that the DNA binding ability of MSX1 is abolished by these two amino acid substitutions. This illustrates a causative role of the T174I and L205R MSX1 homeodomain mutations in tooth agenesis, and suggests that they may influence cell proliferation and differentiation resulting in lesser tooth germ formation in vivo.

Dataset Information

Screening PAX9, MSX1 and WNT10A Mutations in 4 Iranian Families with Non-Syndromic Tooth Agenesis.

Publications

Screening <i>PAX9</i>, <i>MSX1</i> and <i>WNT10A</i> Mutations in 4 Iranian Families with Non-Syndromic Tooth Agenesis.

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