Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia

Hum Genet. 2002 Apr;110(4):371-6. doi: 10.1007/s00439-002-0699-1. Epub 2002 Mar 14.


We recently identified a frame-shift mutation in the PAX9 gene as the underlying cause for hypodontia involving permanent molar teeth segregating in an autosomal dominant pattern in a single large family (Stockton et al. 2000). Here we report a small nuclear family in which a father and his daughter are affected with severe hypodontia, involving agenesis of all primary and permanent molars, evidently caused by deletion of the entire PAX9 gene. Hemizygosity at the PAX9 locus in the two affected individuals was initially discovered when an informative single nucleotide polymorphism, identified while sequencing the gene for mutations, appeared to demonstrate non-Mendelian inheritance. Fluorescence in situ hybridization (FISH) analysis with a cosmid containing the PAX9 gene yielded a signal on only one chromosome 14 homologue and confirmed the presence of a deletion encompassing the PAX9 locus. Analysis of microsatellite loci in the vicinity of PAX9 delineated one breakpoint of the deletion. These data, in concert with FISH analysis with cosmids encompassing a 199 kb region, indicated that the deletion is between approximately 44 kb and 100 kb. PAX9 is one of two genes, and the only odontogenic gene within the deletion interval, thus supporting the model of haploinsufficiency for PAX9 as the underlying basis for hypodontia.

Publication types

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

MeSH terms

  • Anodontia / genetics*
  • Base Sequence
  • DNA Primers
  • DNA-Binding Proteins / genetics*
  • Female
  • Genes, Dominant*
  • Haplotypes
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • PAX9 Transcription Factor
  • Pedigree
  • Transcription Factors / genetics*


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