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

Biason-Lauber, Anna
Böni-Schnetzler, Marianne
Hubbard, Basil P
Published in Cell metabolism. 2013, vol. 17, no. 3, p. 448-55
Abstract 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.
PMID: 23473037
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BIASON-LAUBER, Anna et al. Identification of a SIRT1 mutation in a family with type 1 diabetes. In: Cell metabolism, 2013, vol. 17, n° 3, p. 448-55. doi: 10.1016/j.cmet.2013.02.001 https://archive-ouverte.unige.ch/unige:28879

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Deposited on : 2013-07-11

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