For example, a Leu34Phe missense mutation in human proCART was discovered in obese members of an Italian family across three generations to affect post-translational processing, which coincided with CART peptide deficiency in the sera and reduced resting energy expenditure, ultimately leading to hyperphagia and severe early-onset obesity (del Giudice et al., 2001; Dominguez et al., 2004a; Yanik et al., 2006). This evidence concerns the gene CARTPT and obesity due to melanocortin 4 receptor deficiency.