Identification Of A Novel Single Gene Mutation Causing T1d

Dr. Marc Donath and his colleagues at the University Hospital Basel identified a family with a high frequency of T1D and an inheritance pattern suggesting their diabetes was caused by a single gene mutation. Gene mapping and DNA sequencing of the affected family confirmed that their diabetes was caused by a single gene mutation in the Sirt1 gene. The Sirt1 gene encodes an enzyme that has been associated with several aging-related disorders and is the target of sirtuin activating compounds including the compound called resveratrol (which is found naturally in red wine). These genetic findings suggest that the Sirt1 gene is a critical regulator of diabetes development and that drugs targeting it might have utility in slowing T1D progression.

Ramifications for Individuals with T1D:

This work has identified a novel mechanism that is responsible for a rare genetic form of T1D. More work is required to demonstrate if this mechanism applies to the more common forms of T1D, but if so, there are drugs in development for other indications targeting this pathway that could be useful to slow or prevent progression of T1D. Additional animal work will be required to clarify the potential significance of this finding.

JDRF Involvement:

This work was funded, in part, by a JDRF Strategic Research Agreement to Drs. Donath and Sinclair.

Investigators and Institutions:

This work was led by Dr. Marc Donath and the University Hospital Basel and Dr. David Sinclair at Harvard Medical School.


Biason-Lauber A, Böni-Schnetzler M, and others. Identification of a SIRT1 mutation in a family with type 1 diabetes. Cell Metab. 2013 Mar 5;17(3):448-55.

Hubbard BP, Gomes AP, and others. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. 2013 Mar 8;339(6124):1216-9.