Inactivating mutations in exons 1–13 of the maternal copy of the GNAS gene lead to PHP-Ia, whose phenotype encompasses the Albright Hereditary Osteodystrophy (AHO) signs including short stature (SS), brachydactyly (BR), obesity (OB), round face (RF), subcutaneous ossifications (SO) and mental retardation (MR) together with multiple resistances to PTH (rPTH), TSH (rTSH) and to other aforementioned GPCR-binding hormones. Here, GNAS is linked to obesity due to melanocortin 4 receptor deficiency.