Identification of a SIRT1 mutation in a family with type 1 diabetes

Anna Biason-Lauber, Marianne Böni-Schnetzler, Basil P. Hubbard, Karim Bouzakri, Andrea Brunner, Claudia Cavelti-Weder, Cornelia Keller, Monika Meyer-Böni, Daniel T. Meier, Caroline Brorsson, Katharina Timper, Gil Leibowitz, Andrea Patrignani, Remy Bruggmann, Gino Boily, Henryk Zulewski, Andreas Geier, Jennifer M. Cermak, Peter Elliott, James L. EllisChristoph Westphal, Urs Knobel, Jyrki J. Eloranta, Julie Kerr-Conte, François Pattou, Daniel Konrad, Christian M. Matter, Adriano Fontana, Gerhard Rogler, Ralph Schlapbach, Camille Regairaz, José M. Carballido, Benjamin Glaser, Michael W. McBurney, Flemming Pociot, David A. Sinclair, Marc Y. Donath

Research output: Contribution to journalArticlepeer-review


Type 1 diabetes is caused by autoimmune-mediated β cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to β cell antigens, and a rapid dependence on insulin. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.

Original languageAmerican English
Pages (from-to)448-455
Number of pages8
JournalCell Metabolism
Issue number3
StatePublished - 5 Mar 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology


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