Novel Mutation of the Initiation Codon of <i>PAX9</i> Causes Oligodontia

Klein, Martin; Nieminen, Pekka; Lammi, Laura; Niebuhr, Erik; Kreiborg, Sven

doi:10.1177/154405910508400107

Cited by 107 publications

(95 citation statements)

References 29 publications

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“…Very recently, a mutation in the PAX9 translation initiation codon has been reported (Klein et al, 2005). In the two affected individuals for whom data was provided, there was a history of missing primary teeth, while all of the molars (as well as many other teeth) were absent.…”

Section: Discussionmentioning

confidence: 99%

Novel MSX1 Frameshift Causes Autosomal-dominant Oligodontia

et al. 2006

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Can kindreds with tooth agenesis caused by MSX1 or PAX9 mutations be distinguished by their phenotypes? We have identified an MSX1 frameshift mutation (g.62dupG, p.G22RfsX168) that causes non-syndromic autosomal-dominant oligodontia, featuring the absence of multiple permanent teeth, including all second bicuspids and mandibular central incisors. The dominant phenotype is apparently due to haploinsufficiency. We analyzed patterns of partial tooth agenesis in seven kindreds with defined MSX1 mutations and ten kindreds with defined PAX9 mutations. The probability of missing a particular type of tooth is always bilaterally symmetrical, but differences exist between the maxilla and mandible. MSX1-associated oligodontia typically includes missing maxillary and mandibular second bicuspids and maxillary first bicuspids. The most distinguishing feature of MSX1-associated oligodontia is the frequent (75%) absence of maxillary first bicuspids, while the most distinguishing feature of PAX9-associated oligodontia is the frequent (> 80%) absence of the maxillary and mandibular second molars.

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Section: Discussionmentioning

confidence: 99%

Novel MSX1 Frameshift Causes Autosomal-dominant Oligodontia

et al. 2006

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“…Mutation of the MSX1 and PAX9 gene were identified as the cause of selective tooth agenesis in human, and played a role in early tooth development. [9][10][11][12][13] It affected both primary and permanent teeth, but predominantly involving premolars.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of hypodontia in Chinese orthodontic patients

Rahardjo

2006

Dent. J. (Majalah Kedokteran Gigi)

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“…The presence of inter-and intra-familial variability as it relates to the number and types of missing teeth also suggests that common variants in genes that are involved in tooth signaling may influence the background responsible for the phenotype. To date, several reports have described the association of dominant mutations in MSX1 and PAX9, two transcription factors that are expressed in dental mesenchyme (1,(3)(4)(5)(6)(7)(8)(9)(10)(11). More recently, AXIN2, a Wnt-signaling receptor was identified as responsible for a nonsyndromic form of tooth agenesis (12,13).…”

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confidence: 99%

Functional Consequences of Interactions between Pax9 and Msx1 Genes in Normal and Abnormal Tooth Development

Ogawa

Kapadia

Feng

et al. 2006

Journal of Biological Chemistry

113

104

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Pax9 and Msx1 encode transcription factors that are known to be essential for the switch in odontogenic potential from the epithelium to the mesenchyme. Multiple lines of evidence suggest that these molecules play an important role in the maintenance of mesenchymal Bmp4 expression, which ultimately drives morphogenesis of the dental organ. Here we demonstrate that Pax9 is able to directly regulate Msx1 expression and interact with Msx1 at the protein level to enhance its ability to transactivate Msx1 and Bmp4 expression during tooth development. In addition, we tested how a missense mutation (T62C) in the paired domain of PAX9 that is responsible for human tooth agenesis (1) affects its functions. Our data indicate that although the mutant Pax9 protein (L21P) can bind to the Msx1 protein, it fails to transactivate the Msx1 and Bmp4 promoter, presumably because of its inability to bind cognate paired domain recognition sequences. In addition, synergistic transcriptional activation of the Bmp4 promoter was lost with coexpression of mutant Pax9 and wild-type Msx1. This suggests that Pax9 is critical for the regulation of Bmp4 expression through its paired domain rather than Msx1. Our findings demonstrate the partnership of Pax9 and Msx1 in a signaling pathway that involves Bmp4. Furthermore, the regulation of Bmp4 expression by the interaction of Pax9 with Msx1 at the level of transcription and through formation of a protein complex determines the fate of the transition from bud to cap stage during tooth development.

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Novel Mutation of the Initiation Codon of PAX9 Causes Oligodontia

Cited by 107 publications

References 29 publications

Novel MSX1 Frameshift Causes Autosomal-dominant Oligodontia

Novel MSX1 Frameshift Causes Autosomal-dominant Oligodontia

Prevalence of hypodontia in Chinese orthodontic patients

Functional Consequences of Interactions between Pax9 and Msx1 Genes in Normal and Abnormal Tooth Development

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