Activating Mutations of the Stimulatory G Protein in the McCune–Albright Syndrome

Abstract

Abstract Background. The McCune-Albright syndrome is a sporadic disease characterized by polyostotic fibrous dysplasia, café au lait spots, sexual precocity, and hyperfunction of multiple endocrine glands. These manifestations may be explained by a somatic mutation in affected tissues that results in activation of the signal-transduction pathway generating cyclic AMP (cAMP). We analyzed DNA from tissues of patients with the McCune-Albright syndrome for the presence of activating mutations of the gene for the a subunit of the G protein (Gsα) that stimulates cAMP formation. Methods. Genomic DNA fragments encompassing regions (exons 8 and 9) previously found to contain activating missense mutations of the Gsα gene (gsp mutations) in sporadically occurring pituitary tumors were amplified in tissues from four patients with the McCune-Albright syndrome by the polymerase chain reaction. The amplified DNA was analyzed for mutations by denaturing gradient gel electrophoresis and allele-specific oligonucleotide hyb...