Human Genetics

, Volume 110, Issue 4, pp 371–376

Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia

  • Parimal Das
  • David W. Stockton
  • Christopher Bauer
  • Lisa G. Shaffer
  • Rena N. D’Souza
  • Timothy J. Wright
  • Pragna I. Patel
Original Investigation

DOI: 10.1007/s00439-002-0699-1

Cite this article as:
Das, P., Stockton, D.W., Bauer, C. et al. Hum Genet (2002) 110: 371. doi:10.1007/s00439-002-0699-1

Abstract.

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 ~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.

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Parimal Das
    • 1
  • David W. Stockton
    • 2
  • Christopher Bauer
    • 1
  • Lisa G. Shaffer
    • 2
  • Rena N. D’Souza
    • 4
  • Timothy J. Wright
    • 5
  • Pragna I. Patel
    • 1
  1. 1.Department of Neurology, Baylor College of Medicine, Houston, TX 77030USA
  2. 2.Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030USA
  3. 3.Department of Medicine, Baylor College of Medicine, Houston, TX 77030USA
  4. 4.Department of Orthodontics, Dental Branch, University of Texas Health Science Center, Houston, TX 77030USA
  5. 5.Department of Pediatric Dentistry, University of North Carolina, Chapel Hill, NC 27599USA