The GOOS team have been involved in the publication of a new paper in the journal Diabetes.
Previous work from Prof Sadaf Farooqi’s team established a central role of SH2B1 in the regulation of human energy homeostasis and neurodevelopment. In the present study Prof Farooqi’s lab, in collaboration with Christin Carter-Su and Martin Myers’ groups at the University of Michigan, report the identification of 15 new SH2B1 mutations in patients with severe obesity and a spectrum of neurobehavioral abnormalities, including learning difficulties, aggression and autistic traits. Interestingly, several of these mutations fall within the PH domain of SH2B1 whose specific role has not been definitely established. Disruption of the PH domain in mice resulted in obesity as well as insulin resistance and glucose intolerance beyond that attributable to their increased adiposity. Collectively these findings establish the PH-domain as an important functional feature of SH2B1.