| First Author | Biason-Lauber A | Year | 2013 |
| Journal | Cell Metab | Volume | 17 |
| Issue | 3 | Pages | 448-455 |
| PubMed ID | 23473037 | Mgi Jnum | J:198133 |
| Mgi Id | MGI:5495577 | Doi | 10.1016/j.cmet.2013.02.001 |
| Citation | Biason-Lauber A, et al. (2013) Identification of a SIRT1 mutation in a family with type 1 diabetes. Cell Metab 17(3):448-55 |
| abstractText | Type 1 diabetes is caused by autoimmune-mediated beta 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 beta 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. |
