In addition, we want to mention that the two mutations were respectively detected in an obese subject and a normal-weight subject, which suggested that genetic heterozygosity for a severely dysfunctional IRX3 allele did not determine body weight following a classic Mendelian model, as seen in monogenic genes for obesity such as POMC (Flickinger and Salz, 1994; Krude et al., 1998), MC4R (Vaisse et al., 1998; Yeo et al., 1998), and LEP (Montague et al., 1997; Echwald et al., 1997). Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.