The recent discovery of rare functional mutations in regions of POMC encoding for α-MSH and leading to childhood obesity with no other observed anomalies (in contrast to the POMC mutations previously described [29]) provides support for the use of genetic screens to identify factors upstream and downstream of MC4R in early-onset and severe human obesity [30]. The gene discussed is MC4R; the disease is obesity due to melanocortin 4 receptor deficiency.