Clinical, radiographic, and genetic evaluation of a novel form of autosomal-dominant oligodontia

J Dent Res. 2000 Jul;79(7):1469-75. doi: 10.1177/00220345000790070701.


A frameshift mutation recently identified within the paired domain of the transcription factor, PAX9, has been linked to a unique form of oligodontia in a single, multigenerational family (Stockton et al., 2000). We now describe the phenotypic and segregation analyses of this remarkable kindred, the initial approach taken to identify a candidate gene involved in this form of oligodontia, and the power of this single-family pedigree to generate significant linkage in a genome search. Of the 43 family members enrolled in this study, 21 individuals were affected with several congenitally missing permanent teeth. The pattern of inheritance of the oligodontia trait suggested the involvement of a single gene bearing a dominant mutation. To various degrees, affected members lacked permanent first, second, and third molars in all four quadrants. Several individuals with missing molars also lacked second premolars- most commonly, maxillary second premolars and mandibular central incisors. To the best of our knowledge, this pattern of non-syndromic, familial tooth agenesis has not been previously described in the literature. Since a missense mutation in the homeobox gene, MSX1, was previously linked to tooth agenesis in a single family lacking second premolars and third molars, we performed a mutational analysis of MSX1 by PCR. The absence of a mutation in exons 1 and 2 of MSX1 suggested that allelic mutations in the coding region of MSX1 are not associated with this phenotypically distinct form of oligodontia. Computer simulation of linkage analysis further proved that this pedigree alone was sufficient to generate a significant result for a total genome scan.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Anodontia / diagnostic imaging
  • Anodontia / genetics*
  • Anodontia / pathology
  • Child
  • Computer Simulation
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Female
  • Frameshift Mutation
  • Genes, Dominant
  • Genes, Homeobox
  • Genetic Linkage
  • Homeodomain Proteins / genetics
  • Humans
  • MSX1 Transcription Factor
  • Male
  • PAX9 Transcription Factor
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Radiography
  • Transcription Factors / genetics


  • DNA-Binding Proteins
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • PAX9 Transcription Factor
  • PAX9 protein, human
  • Transcription Factors