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Immunogenetics

, Volume 53, Issue 6, pp 435–439 | Cite as

A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndrome

  • Craig L. Bennett
  • Mary E. Brunkow
  • Fred Ramsdell
  • Kathy C. O'Briant
  • Qili Zhu
  • Ramsay L. Fuleihan
  • Ann O. Shigeoka
  • Hans D. Ochs
  • Phillip F. Chance
Original Paper

Abstract.

The mouse scurfy gene, Foxp3, and its human orthologue, FOXP3, which maps to Xp11.23–Xq13.3, were recently identified by positional cloning. Point mutations and microdeletions of the FOXP3 gene were found in the affected members of eight of nine families with IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked; OMIM 304930). We evaluated a pedigree with clinically typical IPEX in which mutations of the coding exons of FOXP3 were not detected. Our reevaluation of this pedigree identified an A→G transition within the first polyadenylation signal (AAUAAA→AAUGAA) after the stop codon. The next polyadenylation signal is not encountered for a further 5.1 kb. This transition was not detected in over 212 normal individuals (~318 X chromosomes), excluding the possibility of a rare polymorphism. We suggest that this mutation is causal of IPEX in this family by a mechanism of nonspecific degradation of the FOXP3 gene message.

IPEX Polyadenylation T-cell activation FOXP3 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Craig L. Bennett
    • 1
  • Mary E. Brunkow
    • 2
  • Fred Ramsdell
    • 2
  • Kathy C. O'Briant
    • 1
  • Qili Zhu
    • 3
  • Ramsay L. Fuleihan
    • 4
  • Ann O. Shigeoka
    • 5
  • Hans D. Ochs
    • 3
  • Phillip F. Chance
    • 1
  1. 1.Division of Genetics and Development, Department of Pediatrics, University of Washington School of Medicine, Box 356320, Seattle, WA 98195, USA
  2. 2.Celltech R&D, Seattle Research Facility, 1631 220th Street South East, Bothell, WA 98021, USA
  3. 3.Division of Immunology, Infectious Disease and Rheumatology, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
  4. 4.Department of Pediatrics, Yale University School of Medicine, CT 06520-8081, USA
  5. 5.Department of Pediatrics, University of Utah School of Medicine, 100 North Medical Drive, Salt Lake City, UT 84113, USA

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