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.