Mutations that affect exons 1–13 of GNAS and directly reduce expression or function of Gsα are the basis for tissue resistance to multiple hormones plus features of Albright hereditary osteodystrophy (AHO) in patients with PHP1A (OMIM 103580, also termed iPPSD type 2; ref. 2) when they are on the maternal allele and for pseudopseudohypoparathyroidism (PPHP; OMIM 612463), characterized by AHO only, when they lie on the paternal allele (20, 21). Here, GNAS is linked to pseudopseudohypoparathyroidism.