By screening children with severe, young-onset obesity for the genetic defects identified in mice, loss-of-function (LOF) mutations causing deficiencies are found in genes encoding for appetite-regulating hormones or their receptors such as leptin (LEP) [6], leptin receptor (LEPR) [7], proopiomelanocortin (POMC) [8], and melanocortin 4 receptor (MC4R) [9]. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.