Learning from extreme patient phenotypes

Our identification of novel traits and variants for monogenic obesity has several implications: i) We need to revise diagnostic algorithms to identify these patients. ii) We can understand human pathophysiology. iii) We need new treatment options. We address these challenges by developing new diagnostic tools. From in depth characterization (metabolic chamber, fMRI) of patients with distinct severe phenotypes, we uncover new pathophysiological mechanisms. We explore the underlying mechanisms using induced pluripotent stem cells (iPSCs) from affected patients and experimental humanized animal models. This translational approach may ultimately inform new treatment strategies, which we have already started to test.