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Identification of a SIRT1 Mutation in a Family with Type 1 Diabetes

  • Lauber-Biason, Anna Department of Medicine, University of Fribourg, Switzerland
  • Böni-Schnetzler, Marianne Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Hubbard, Basil P. Department of Genetics, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, USA
  • Bouzakri, Karim Department of Genetic Medicine and Development, University of Geneva, Switzerland
  • Brunner, Andrea Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Cavelti-Weder, Claudia Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Keller, Cornelia Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Meyer-Böni, Monika Department of Medicine, University of Fribourg, Switzerland
  • Meier, Daniel T. Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Brorsson, Caroline Glostrup Research Institute, Glostrup University Hospital, Denmark
  • Timper, Katharina Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Leibowitz, Gil Endocrinology and Metabolism Service, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
  • Patrignani, Andrea Functional Genomic Center Zurich, Federal Institute of Technology, University of Zurich, Switzerland
  • Bruggmann, Rémy Functional Genomic Center Zurich, Federal Institute of Technology, University of Zurich, Switzerland
  • Boily, Gino University of Ottawa, Canada
  • Zulewski, Henryk Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Geier, Andreas Gastroenterology and Hepatology, Center of Integrative Human Physiology and University Hospital Zurich, Switzerland
  • Cermak, Jennifer M. Sirtris, a GSK company, Cambridge, USA
  • Elliott, Peter Sirtris, a GSK company, Cambridge, USA
  • Ellis, James L. Sirtris, a GSK company, Cambridge, USA
  • Westphal, Christoph Sirtris, a GSK company, Cambridge, USA
  • Knobel, Urs Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
  • Eloranta, Jyrki J. Department of Clinical Pharmacology and Toxicology, Center of Integrative Human Physiology and University Hospital Zurich, Switzerland
  • Kerr-Conte, Julie University Lille Nord de France, France
  • Pattou, François University Lille Nord de France, France
  • Konrad, Daniel University Children’s Hospital, Zurich, Switzerland
  • Matter, Christian M. Department of Cardiology, Center of Integrative Human Physiology and University Hospital Zurich, Switzerland
  • Fontana, Adriano Institute of Experimental Immunology, University of Zurich, Switzerland
  • Rogler, Gerhard Gastroenterology and Hepatology, Center of Integrative Human Physiology and University Hospital Zurich, Switzerland
  • Schlapbach, Ralph Functional Genomic Center Zurich, Federal Institute of Technology, University of Zurich, Switzerland
  • Regairaz, Camille Novartis Institutes for BioMedical Research, Switzerland
  • Carballido, José M. Novartis Institutes for BioMedical Research, Switzerland
  • Glaser, Benjamin Endocrinology and Metabolism Service, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
  • McBurney, Michael W. University of Ottawa, Canada
  • Pociot, Flemming Glostrup Research Institute, Glostrup University Hospital, Denmark
  • Sinclair, David A. Department of Genetics, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, USA
  • Donath, Marc Y. Endocrinology, Diabetes, and Metabolism, and Department of Biomedicine, University Hospital Basel, Switzerland
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    05.03.2013
Published in:
  • Cell Metabolism. - 2013, vol. 17, no. 3, p. 448-455
English 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
Faculty
Faculté des sciences et de médecine
Department
Médecine 3ème année
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/302903
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