Biason-Lauber, Anna, Böni-Schnetzler, Marianne, Hubbard, Basil P, Bouzakri, Karim, Brunner, Andrea, Cavelti-Weder, Claudia, Keller, Cornelia, Meyer-Böni, Monika, Meier, Daniel T, Brorsson, Caroline, Timper, Katharina, Leibowitz, Gil, Patrignani, Andrea, Bruggmann, Remy, Boily, Gino, Zulewski, Henryk, Geier, Andreas, Cermak, Jennifer M, Elliott, Peter, Ellis, James L, Westphal, Christoph, Knobel, Urs, Eloranta, Jyrki J, Kerr-Conte, Julie, Pattou, François, Konrad, Daniel, Matter, Christian M, Fontana, Adriano, Rogler, Gerhard, Schlapbach, Ralph, Regairaz, Camille, Carballido, Jose, Glaser, Benjamin, McBurney, Michael W, Pociot, Flemming, Sinclair, David A and Donath, Marc Y (2012) Identification of a SIRT1 mutation in a family with Type 1 Diabetes. Cell Metabolism, 17 (3). pp. 448-455. ISSN 1550-4131

Abstract

Type 1 diabetes is caused by autoimmune-mediated
b 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 b 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.§

Item Type:	Article
Keywords:	Type 1 diabetes, genetics, Sirtuin-1, metabolism
Date Deposited:	13 Oct 2015 13:15
Last Modified:	13 Oct 2015 13:15
URI:	https://oak.novartis.com/id/eprint/5451