Genetic and molecular aspects of McCune-Albright syndrome

McCune-Albright syndrome (MAS) is characterized by the clinical triad of polyostotic fibrous dysplasia, café-au-lait pigmented skin lesions and endocrinopathy (1,2) The molecular lesion in MAS is a postzygotic mutation in the GNAS gene that leads to activation of Gsalpha, the alpha chain of the heterotrimeric G protein, Gsalpha. Cells that carry the activating mutation are distributed in a mosaic pattern. A clinical diagnosis of MAS can be made when a patient is found to have at least two features of the classical triad (3). Because of the restricted pattern of distribution of the GNAS mutation, termed gsp, initial molecular analyses were limited to lesional tissue, but recent techniques such as peptide nucleic acid clamping have improved the sensitivity of current assays and now enable the detection of gsp mutations in circulating cells from many patients with MAS.