Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus (original) (raw)

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Acknowledgements

We thank all subjects for participation in this study. We thank W.L. Gross, E. Gromnica-Ihle, H.-H. Peter, S. Schnarr and M. Linné for clinical assistance. We acknowledge technical assistance of C. Flachmeier, M. Schwarz and A. Müller. We thank M. Weber at the Technische Universität Dresden confocal microscopy core facility. We thank M.T. Pisabarro, K. Köhler, M.C. Cardoso and F.C. Luft for helpful discussions and comments. This work was supported by a Marie Curie Development Host Fellowship from the European Commission to M.A.L.-K., a grant from the German Ministry of Science and Education (BMBF Kompetenznetz Rheuma C2.12) to T.W., US National Institutes of Health (NIH) grant AI45587 to J.L., NIH grant GM069962 to F.W.P. and a grant-in-aid from the National Genome Research Network (NGFN2) of the German Ministry of Science and Education (BMBF) to Y.-A.L. and N.H.

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Author notes

1. Maolian Gong, Dipanjan Chowdhury, Lydia Senenko, Kerstin Engel and Young-Ae Lee: These authors contributed equally to this work.

Authors and Affiliations

1. Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, Dresden, 01307, Germany
   Min Ae Lee-Kirsch, Lydia Senenko, Kerstin Engel & Manfred Gahr
2. Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, 13125, Germany
   Maolian Gong, Young-Ae Lee, Oliver Hummel, Klaus Rohde & Norbert Hübner
3. Department of Pediatrics, CBR Institute for Biomedical Research, Harvard Medical School, Boston, 02125, Massachusetts, USA
   Dipanjan Chowdhury & Judy Lieberman
4. Charité - Universitätsmedizin Berlin, Pediatric Pneumology and Immunology, Campus Virchow-Klinikum, Berlin, 13353, Germany
   Young-Ae Lee
5. Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston-Salem, 27157, North Carolina, USA
   Udesh de Silva, Suzanna L Bailey & Thomas Hollis
6. Medizinische Hochschule Hannover, Klinische Immunologie, Hannover, 30625, Germany
   Torsten Witte & Reinhold E Schmidt
7. Imperial College, Faculty of Medicine, Section of Rheumatology and Molecular Genetics, Hammersmith Hospital, London, W12 0NN, UK
   Timothy J Vyse & Andrew Wong
8. Department of Biosciences and Nutrition, Karolinska Institute, and Clinical Research Centre, Huddinge, 14157, Sweden
   Juha Kere
9. Klinik für Dermatologie, Technische Universität Dresden, Dresden, 01307, Germany
   Christiane Pfeiffer
10. Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, 27157, North Carolina, USA
    Scott Harvey & Fred W Perrino
11. Department of Medical Genetics, University of Helsinki, Helsinki, 00014, Finland
    Sari Koskenmies
12. Department of Dermatology, 00014, Helsinki, Finland
    Sari Koskenmies
13. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK
    Anna F Dominiczak

Authors

1. Min Ae Lee-Kirsch
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2. Maolian Gong
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3. Dipanjan Chowdhury
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4. Lydia Senenko
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5. Kerstin Engel
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6. Young-Ae Lee
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7. Udesh de Silva
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8. Suzanna L Bailey
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9. Torsten Witte
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10. Timothy J Vyse
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11. Juha Kere
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12. Christiane Pfeiffer
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13. Scott Harvey
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14. Andrew Wong
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15. Sari Koskenmies
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16. Oliver Hummel
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17. Klaus Rohde
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18. Reinhold E Schmidt
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19. Anna F Dominiczak
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20. Manfred Gahr
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21. Thomas Hollis
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22. Fred W Perrino
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23. Judy Lieberman
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24. Norbert Hübner
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Contributions

M.A.L.-K. developed the project. M.A.L.-K. and N.H. codirected the project. M.G., K.E., L.S., Y.-A.L. and O.H. performed mutation screening. F.W.P., U.d.S., S.L.B., S.H. and T.H. generated bacterial expression constructs, performed biochemical analysis of recombinant TREX1 and generated the structural model of TREX1. L.S. and K.E. generated mammalian expression constructs and performed transfection and immune histochemistry. D.C. and J.L. performed studies on granzyme A–mediated apoptosis. T.J.V., A.W., J.K., S.K., T.W., R.E.S., A.F.D., M.G. and C.P. contributed individuals with SLE or controls. K.R. performed statistical analysis. M.A.L.-K. wrote the paper with J.L. and N.H.

Corresponding authors

Correspondence toMin Ae Lee-Kirsch or Norbert Hübner.

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The authors declare no competing financial interests.

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Lee-Kirsch, M., Gong, M., Chowdhury, D. et al. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus.Nat Genet 39, 1065–1067 (2007). https://doi.org/10.1038/ng2091

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• Received: 20 February 2007
• Accepted: 29 May 2007
• Published: 29 July 2007
• Issue Date: September 2007
• DOI: https://doi.org/10.1038/ng2091