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

Lee-Kirsch, M. A. et al. (2007) Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nature Genetics, 39(9), pp. 1065-1067. (doi: 10.1038/ng2091) (PMID:17660818)

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= 4.1x10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dominiczak, Professor Anna
• Authors: Lee-Kirsch, M. A., Gong, M., Chowdhury, D., Senenko, L., Engel, K., Lee, Y.-A., de Silva, U., Bailey, S. L., Witte, T., Vyse, T. J., Kere, J., Pfeiffer, C., Harvey, S., Wong, A., Koskenmies, S., Hummel, O., Rohde, K., Schmidt, R. E., Dominiczak, A. F., Gahr, M., Hollis, T., Perrino, F. W., Lieberman, J., and Hubner, N.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 29 July 2007