Brief Communication abstract
Nature Genetics 39, 1065 - 1067 (2007)
Published online: 29 July 2007 | doi:10.1038/ng2091
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus
Min Ae Lee-Kirsch1, Maolian Gong2,14, Dipanjan Chowdhury3,14, Lydia Senenko1,14, Kerstin Engel1,14, Young-Ae Lee2,4,14, Udesh de Silva5, Suzanna L Bailey5, Torsten Witte6, Timothy J Vyse7, Juha Kere8, Christiane Pfeiffer9, Scott Harvey10, Andrew Wong7, Sari Koskenmies11,12, Oliver Hummel2, Klaus Rohde2, Reinhold E Schmidt6, Anna F Dominiczak13, Manfred Gahr1, Thomas Hollis5, Fred W Perrino10, Judy Lieberman3 & Norbert Hübner2
TREX1 acts in concert with the SET complex in granzyme A–mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières 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 
10-7). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.
- Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, 01307 Dresden, Germany.
- Max Delbrück Center for Molecular Medicine (MDC), 13125 Berlin-Buch, Germany.
- CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02125, USA.
- Charité - Universitätsmedizin Berlin, Pediatric Pneumology and Immunology, Campus Virchow-Klinikum, 13353 Berlin, Germany.
- Center for Structural Biology, Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA.
- Medizinische Hochschule Hannover, Klinische Immunologie, 30625 Hannover, Germany.
- Imperial College, Faculty of Medicine, Section of Rheumatology and Molecular Genetics, Hammersmith Hospital, London W12 0NN, UK.
- Karolinska Institute, Department of Biosciences and Nutrition, and Clinical Research Centre, 14157 Huddinge, Sweden.
- Klinik für Dermatologie, Technische Universität Dresden, 01307 Dresden, Germany.
- Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA.
- University of Helsinki, Department of Medical Genetics, 00014 Helsinki, Finland.
- Department of Dermatology, 00014 Helsinki, Finland.
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
- These authors contributed equally to this work.
Correspondence to: Min Ae Lee-Kirsch1 e-mail: minae.lee-kirsch@uniklinikum-dresden.de
Correspondence to: Norbert Hübner2 e-mail: nhuebner@mdc-berlin.de
