An unusual presentation of McCune-Albright syndrome confirmed by an activating mutation of the Gs alpha-subunit from a bone lesion.

The McCune-Albright syndrome (MAS) is characterized clinically by polyostotic fibrous dysplasia, café-au-lait skin lesions, sexual precocity, and various other endocrinopathies. Recent investigations suggest an etiological role for embryonic somatic missense mutations that predict the substitution of a His or Cys for Arg at amino acid 201 of the Gs alpha-subunit (Gs alpha). Identification of these mutations in affected tissues is a sensitive assay that may help define a more complete clinical spectrum of the MAS. We investigated a woman who developed fibrous dysplasia 24 yr after premature menstruation. To determine if this was an unusual MAS variant, DNA and RNA were analyzed from affected and unaffected tissues. From samples of affected rib and normal rib DNA was extracted, amplified by polymerase chain reaction, subcloned, and sequenced. RNA was extracted from affected bone, reverse transcribed, amplified by polymerase chain reaction, subcloned, and sequenced. DNA sequence predicting a His for Arg substitution at Gs alpha amino acid 201 was found in 47% of the recombinant plasmids from DNA of affected bone and 17% of the plasmids from DNA of unaffected bone; a significant (P < 0.05) difference in frequency. The His201 substitution was found in 42% of the recombinant plasmids from RNA of affected bone. We conclude that this clinical variant is qualitatively indistinguishable from presentations of the complete MAS.