Editor—Fibrous dysplasia of bone is a sporadic developmental condition characterised by intense marrow fibrosis and increased rates of bone turnover. Mutations of the gene encoding the α subunit of the stimulatory guanine nucleotide binding protein (GNAS1) linked to adenylate cyclase have been described in bone cells from patients with McCune-Albright syndrome.1 2 The mutations identified are missense point mutations within exon 8 that result in a substitution of histidine or cysteine for arginine at amino acid 201 (R201H or R201C). Both mutations lead to the constitutive activation of adenylate cyclase resulting in increased signalling through the cyclic AMP (cAMP) pathway. While the cause of fibrous dysplasia of bone has been clarified by the discovery of GNAS1mutations in bone cells, the pathogenesis of the characteristic finding of bone lesions is as yet unclear. We have performed molecular analysis of cultured cells isolated from the periosteum and hypertrophic endosteal membrane of the identical area in a patient with severe polyostotic fibrous dysplasia associated …