We recently expanded on our understanding of how genetic alterations in SH2B1 contribute to obesity and neurobehavioral difficulties.
Research previously carried out by our team identified a small number of obese individuals whose SH2B1 gene was disrupted by a mutation. We found that those mutations were a strong contributing factor to their high body weight, as well as a set of neurobehavioral problems. In a new study published this month we report the identification of another 15 individuals who carry a mutation in the SH2B1 gene. They suffer from a spectrum of neurobehavioral difficulties, including learning difficulties, dyspraxia, hyperactivity, aggression and autistic traits. Interestingly, several of the newly discovered mutations in SH2B1 cluster around a specific section of the gene (‘PH-domain’) whose specific biological role is not understood. Our collaborator Dr Carter-Su (University of Michigan, USA) and her team used mice to investigate the effect of PH-domain disruption on the function of SH2B1 and found that it plays an important role, since mice with a damaged PH-domain became obese and diabetic.