Novel missense mutation in PAX9 gene associated with familial tooth agenesis

Junior, Breno Ramos Boeira; Echeverrigaray, Sérgio

doi:10.1111/j.1600-0714.2012.01193.x

Cited by 21 publications

(4 citation statements)

References 29 publications

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“…Several genes, such as EDA, MSX1, PAX9, WNT10A, and WNT10B, have been identified as causative for non-syndromic human tooth agenesis [1][2][3][4][5]. Germline pathogenic variants (GPVs) in each of these causative genes lead to tooth deficiencies, and the sites of tooth defects, produced by each gene, are distinctive.…”

Section: Introductionmentioning

confidence: 99%

Effects of Wnt10a and Wnt10b Double Mutations on Tooth Development

Yoshinaga

Yasue

Mitsui

et al. 2023

Genes

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WNT molecules are the regulators of various biological functions, including body axis formation, organ development, and cell proliferation and differentiation. WNTs have been extensively studied as causative genes for an array of diseases. WNT10A and WNT10B, which are considered to be genes of the same origin, have been identified as causative genes for tooth deficiency in humans. However, the disrupted mutant of each gene does not show a decrease in teeth number. A negative feedback loop, interacting with several ligands based on a reaction–diffusion mechanism, was proposed to be important for the spatial patterning of tooth formation, and WNT ligands have been considered to play a pivotal role in controlling tooth patterning from mutant phenotypes of LDL receptor-related proteins (LRPs) and WNT co-receptors. The Wnt10a and Wnt10b double-mutants demonstrated severe root or enamel hypoplasia. In Wnt10a−/− and Wnt10a+/−;Wnt10b−/− mice, changes in the feedback loop may collapse the modulation of fusion or split a sequence of tooth formation. However, in the double-knockout mutant, a decrease in the number of teeth was observed, including the upper incisor or third molar in both jaws. These findings suggest that there may be a functional redundancy between Wnt10a and Wnt10b and that the interaction between the two genes functions in conjunction with other ligands to control the spatial patterning and development of teeth.

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Section: Introductionmentioning

confidence: 99%

Effects of Wnt10a and Wnt10b Double Mutations on Tooth Development

Yoshinaga

Yasue

Mitsui

et al. 2023

Genes

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“…The genotypes of 193 patients with 74 PAX9 variants are shown in Supplementary Table S1 ( Stockton et al, 2000 ; Nieminen et al, 2001 ; Das et al, 2002 ; Frazier-Bowers et al, 2002 ; Boyadjiev et al, 2003 ; Das et al, 2003 ; Lammi et al, 2003 ; Mostowska et al, 2003 ; Jumlongras et al, 2004 ; Klein et al, 2005 ; Zhao et al, 2005 ; Kapadia et al, 2006 ; Mostowska et al, 2006 ; Hansen et al, 2007 ; Tallón-Walton et al, 2007 ; Zhao et al, 2007 ; Guala et al, 2008 ; Wang et al, 2009a ; Wang et al, 2009b ; Haldeman-Englert et al, 2010 ; Pawlowska et al, 2010 ; Bergendal et al, 2011 ; Mendoza-Fandino et al, 2011 ; Paixão-Côrtes et al, 2011 ; Suda et al, 2011 ; Wang et al, 2011 ; Liang et al, 2012 ; Wang et al, 2012 ; Zhu et al, 2012 ; Mostowska et al, 2013a ; Arte et al, 2013 ; Mostowska et al, 2013b ; Boeira and Echeverrigaray, 2013 ; Mitsui et al, 2014 ; Thimmegowda et al, 2015 ; Haddaji Mastouri et al, 2016 ; Liang et al, 2016 ; Shahid et al, 2016 ; Yu et al, 2016 ; Choi et al, 2017 ; Daw et al, 2017 ; Murakami et al, 2017 ; Wong et al, 2018 ; Sun et al, 2021 ). We found that PAX9 -related NSO accounted for 78.2% of the 193 patients, non-syndromic hypodontia for 18.1%, and syndromic oligodontia account for 2.6%.…”

Section: Resultsmentioning

confidence: 99%

Genotype-phenotype pattern analysis of pathogenic PAX9 variants in Chinese Han families with non-syndromic oligodontia

et al. 2023

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Background: Non-syndromic oligodontia is characterized by the absence of six or more permanent teeth, excluding third molars, and can have aesthetic, masticatory, and psychological consequences. Previous studies have shown that PAX9 is associated with autosomal dominant forms of oligodontia but the precise molecular mechanisms are still unknown.Methods: Whole-exome and Sanger sequencing were performed on a cohort of approximately 28 probands with NSO, for mutation analysis. Bioinformatic analysis was performed on the potential variants. Immunofluorescence assay, western blotting, and qPCR were used to explore the preliminary functional impact of the variant PAX9 proteins. We reviewed PAX9-related NSO articles in PubMed to analyze the genotype-phenotype correlations.Results: We identified three novel PAX9 variants in Chinese Han families: c.152G>T (p.Gly51Val), c.239delC (p.Thr82Profs*3), and c.409C>T (q.Gln137Ter). In addition, two previously reported missense variants were identified: c.140G>C (p.Arg47Pro) and c.146C>T (p.Ser49Leu) (reference sequence NM_006194.4). Structural modeling revealed that all missense variants were located in the highly conserved paired domain. The other variants led to premature termination of the protein, causing structural impairment of the PAX9 protein. Immunofluorescence assay showed abnormal subcellular localizations of the missense variants (R47P, S49L, and G51V). In human dental pulp stem cells, western blotting and qPCR showed decreased expression of PAX9 variants (c.140G>C, p.R47P, and c.152G>T, p.G51V) compared with the wild-type group at both the transcription and translation levels. A review of published papers identified 64 PAX9 variants related to NSO and found that the most dominant feature was the high incidence of missing upper second molars, first molars, second premolars, and lower second molars.Conclusion: Three novel PAX9 variants were identified in Chinese Han families with NSO. These results extend the variant spectrum of PAX9 and provide a foundation for genetic diagnosis and counseling.

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“…First genes identified in tooth agenesis were reported to be PAX-9 (paired box 9) and MSX-1 (muscle segment homeobox 1). 32,33 Many different mutations in genes such as MSX-1 and PAX-9 might cause tooth agenesis. It was reported that MSX-1 and PAX-9 play a significant role in mediating direct epithelial-mesenchymal interactions during in the early stages of tooth development especially bud and cap stages.…”

Section: Genetic Factorsmentioning

confidence: 99%

Current Approaches for Tooth Agenesis: A Review

Şentürk¹,

Güzel²

2018

Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi

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Hypodontia is defined as the congenital deficiency of one or more teeth and is one of the most common dental anomalies in humans. Multifactorial etiology can include environmental factors as well, since a combination of environmental and genetic factors might contribute to the occurrence of dental agenesis. Patient with missing teeth; reduced masticatory ability, inarticulate pronunciation may encounter esthetics and periodontal problems. Tooth agenesis definition, etiology, genes that cause tooth agenesis and treatment of tooth agenesis is mentioned in this review. Nowadays, many genes which play role in tooth development reported to be a potential candidate gene in tooth agenesis. Functional changes seen in genes which play role in tooth agenesis are mentioned that there may be a relationship with the development of cancer and tooth agenesis may be a significant marker for cancer.

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Novel missense mutation in PAX9 gene associated with familial tooth agenesis

Cited by 21 publications

References 29 publications

Effects of Wnt10a and Wnt10b Double Mutations on Tooth Development

Effects of Wnt10a and Wnt10b Double Mutations on Tooth Development

Genotype-phenotype pattern analysis of pathogenic PAX9 variants in Chinese Han families with non-syndromic oligodontia

Current Approaches for Tooth Agenesis: A Review

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