A de novo balanced translocation between chromosomes 1p22.1 and 6q16.2, which disrupts SIM1 (Holder et al. 2000), and missense mutations in SIM1 cause severe obesity and a variable phenotype of developmental delay (Ramachandrappa et al. 2013). The gene discussed is SIM1; the disease is obesity due to melanocortin 4 receptor deficiency.