AN UNUSUAL PRESENTATION OF MCCUNE-ALBRIGHT SYNDROME CONFIRMED BY AN ACTIVATING MUTATION OF THE G(S) ALPHA-SUBUNIT FROM A BONE LESION

The McCune-Albright syndrome (MAS) is characterized clinically by poly ostotic fibrous dysplasia, cafe-au-lait skin lesions, sexual precocity , and various other endocrinopathies. Recent investigations suggest an etiological role for embryonic somatic missense mutations that predic t the substitution of a His or Cys for Arg at amino acid 201 of the G( s) alpha-subunit (G(s) alpha). Identification of these mutations in af fected tissues is a sensitive assay that may help define a more comple te 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 affec ted and unaffected tissues. From samples of affected rib and normal ri b DNA was extracted, amplified by polymerase chain reaction, subcloned , and sequenced. RNA was extracted from affected bone, reverse transcr ibed, amplified by polymerase chain reaction, subcloned, and sequenced . DNA sequence predicting a His for Arg substitution at G(s) alpha ami no acid 201 was found in 47% of the recombinant plasmids from DNA of a ffected bone; and 17% of the plasmids from DNA of unaffected bone; a s ignificant (P < 0.05) difference in frequency. The His(201) substituti on was found in 42% of the recombinant plasmids from RNA of affected b one. We conclude that this clinical variant is qualitatively indisting uishable from presentations of the complete MAS.