Dynamics of Ovarian Function in an Adult Woman with McCune-Albright Syndrome1

McCune-Albright syndrome is a sporadic disease characterized by polyostotic fibrous dysplasia cafe´-aux-lait lesions and a variety of endocrine disorders. The molecular basis of this syndrome has recently been elucidated. Missense point mutations in the GNAS1 gene located on the long arm of chromosome 20 and encoding for the asubunit of Gs (the G protein that stimulates cAMP) of transmembrane glycoprotein receptors have been identified. Mutations at codon 201 substituting Arg with either Cys or His give rise to abnormal Gsaproteins that reduce the intrinsic guanosine triphosphatase activity thereby constitutively activating the Gs protein. The mutation is found in variable abundance in different endocrine and nonendocrine tissues consistent with the mosaic distribution of abnormal cells generated by a somatic cell mutation early in embryogenesis. Severe disease may be associated with an earlier mutational event leading to more widespread distribution of mutated cells. (excerpt)