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

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, Rémy; Boily, Gino; Zulewski, Henryk; Geier, Andreas; Cermak, Jennifer M; Elliott, Peter; Ellis, James L.; ... (2013). Identification of a SIRT1 mutation in a family with type 1 diabetes. Cell metabolism, 17(3), pp. 448-455. Cell Press 10.1016/j.cmet.2013.02.001

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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.

Item Type:

Journal Article (Original Article)

UniBE Contributor:

Bruggmann, Rémy

ISSN:

1550-4131

Publisher:

Cell Press

Language:

English

Submitter:

Rémy Bruggmann

Date Deposited:

09 Jul 2014 15:14

Last Modified:

27 Dec 2014 02:13

Publisher DOI:

10.1016/j.cmet.2013.02.001

PubMed ID:

23473037

BORIS DOI:

10.7892/boris.47851

URI:

https://boris.unibe.ch/id/eprint/47851

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