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Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus

Authors

  • M.A. Lee-Kirsch
  • M. Gong
  • D. Chowdhury
  • L. Senenko
  • K. Engel
  • Y.A. Lee
  • U. de Silva
  • S.L. Bailey
  • T. Witte
  • T.J. Vyse
  • J. Kere
  • C. Pfeiffer
  • S. Harvey
  • A. Wong
  • S. Koskenmies
  • O. Hummel
  • K. Rohde
  • R.E. Schmidt
  • A.F. Dominiczak
  • M. Gahr
  • T. Hollis
  • F.W. Perrino
  • J. Lieberman
  • N. Huebner

Journal

  • Nature Genetics

Citation

  • Nat Genet 39 (9): 1065-1067

Abstract

  • TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutieres syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3 UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.


DOI

doi:10.1038/ng2091