Human Genetics

, Volume 114, Issue 3, pp 242–249

A novel missense mutation in the paired domain of PAX9 causes non-syndromic oligodontia

  • Dolrudee Jumlongras
  • Jenn-Yih Lin
  • Anas Chapra
  • Christine E. Seidman
  • Jonathan G. Seidman
  • Richard L. Maas
  • Bjorn R. Olsen
Original Investigation

DOI: 10.1007/s00439-003-1066-6

Cite this article as:
Jumlongras, D., Lin, JY., Chapra, A. et al. Hum Genet (2004) 114: 242. doi:10.1007/s00439-003-1066-6

Abstract

PAX9, a paired domain transcription factor, has important functions in craniofacial and limb development. Heterozygous mutations of PAX9, including deletion, nonsense, or frameshift mutations that lead to a premature stop codon, and missense mutations, were previously shown to be associated with autosomal dominant oligodontia. Here, we report a novel missense mutation that lies in the highly conserved paired domain of PAX9 and that is associated with non-syndromic oligodontia in one family. The mutation, 83G→C, is predicted to result in the substitution of arginine by proline (R28P) in the N-terminal subdomain of PAX9 paired domain. To rule out the possibility that this substitution is a rare polymorphism and to test whether the predicted amino acid substitution disrupts protein-DNA binding, we analyzed the binding of wild-type and mutant PAX9 paired domain to double-stranded DNA targets. The R28P mutation dramatically reduces DNA binding of the PAX9 paired domain and supports the hypothesis that loss of DNA binding is the pathogenic mechanism by which the mutation causes oligodontia.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Dolrudee Jumlongras
    • 1
    • 2
    • 3
    • 5
    • 6
  • Jenn-Yih Lin
    • 5
  • Anas Chapra
    • 5
  • Christine E. Seidman
    • 4
  • Jonathan G. Seidman
    • 4
  • Richard L. Maas
    • 3
  • Bjorn R. Olsen
    • 1
    • 2
  1. 1.Department of Cell BiologyHarvard Medical SchoolBostonUSA
  2. 2.Department of Oral and Developmental BiologyHarvard School of Dental MedicineBostonUSA
  3. 3.Division of Genetics, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  4. 4.Department of GeneticsHarvard Medical SchoolBostonUSA
  5. 5.Department of Pediatric DentistryTufts University School of Dental MedicineBostonUSA
  6. 6.New Research Building, Room 458Harvard Medical SchoolBostonUSA

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