Biason-Lauber, AnnaAnnaBiason-LauberBöni-Schnetzler, MarianneMarianneBöni-SchnetzlerHubbard, Basil P.Basil P.HubbardBouzakri, KarimKarimBouzakriBrunner, AndreaAndreaBrunnerCavelti-Weder, ClaudiaClaudiaCavelti-WederKeller, CorneliaCorneliaKellerMeyer-Böni, MonikaMonikaMeyer-BöniMeier, Daniel T.Daniel T.MeierBrorsson, CarolineCarolineBrorssonTimper, KatharinaKatharinaTimperLeibowitz, GilGilLeibowitzPatrignani, AndreaAndreaPatrignaniBruggmann, RémyRémyBruggmannBoily, GinoGinoBoilyZulewski, HenrykHenrykZulewskiGeier, AndreasAndreasGeierCermak, Jennifer MJennifer MCermakElliott, PeterPeterElliottEllis, James L.James L.EllisWestphal, ChristophChristophWestphalKnobel, UrsUrsKnobelEloranta, Jyrki J.Jyrki J.ElorantaKerr-Conte, JulieJulieKerr-ContePattou, FrançoisFrançoisPattouKonrad, DanielDanielKonradMatter, Christian M.Christian M.MatterFontana, AdrianoAdrianoFontanaRogler, GerhardGerhardRoglerSchlapbach, RalphRalphSchlapbachRegairaz, CamilleCamilleRegairazCarballido, José M.José M.CarballidoGlaser, BenjaminBenjaminGlaserMcBurney, Michael W.Michael W.McBurneyPociot, FlemmingFlemmingPociotSinclair, David A.David A.SinclairDonath, Marc Y.Marc Y.Donath2024-10-152024-10-152013-03-05https://boris-portal.unibe.ch/handle/20.500.12422/118796Type 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.enarticle10.7892/boris.478512347303710.1016/j.cmet.2013.02.001