In conclusion, by employing a novel and unique strategy for whole-exome capture and sequencing analysis of two trios comprised of patients with severe early-onset obesity, we have identified sequence variants in the LRP2 and in the UCP2 genes that might explain the phenotype of a patient with severe early-onset obesity, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and idiopathic hyperprolactinaemia. The gene discussed is LRP2; the disease is Central hypothyroidism.