Primary hyperparathyroidism-associated polyostotic fibrous dysplasia: absence of McCune-Albright syndrome mutations.

Several cases of sporadic primary hyperparathyroidism in association with fibrous dysplasia of the bone have been reported in the English literature. Since fibrous dysplasia is a major feature and hyperparathyroidism is occasionally found in the McCune-Albright syndrome, we hypothesized that such cases may represent a variant of this syndrome. A 28-year-old male had primary hyperparathyroidism associated with polyostotic fibrous dysplasia but no other manifestations of the McCune-Albright syndrome. Genomic DNA samples from his parathyroid adenoma, dysplastic bone sample, and peripheral leukocytes were analyzed for the presence of activating mutations of the stimulating G protein alpha subunit gene (gsp). Allele-specific hybridization revealed the presence of normal sequences only, coding for arginine and glutamine at codons 201 (exon 8) and 227 (exon 9), respectively. Further, single strand conformational analysis of a 224 base pair fragment of exon 8 revealed no conformational aberrations. Furthermore, the sequences of a 164 base pair fragment of exon 8 and a 170 base pair fragment of exon 9 were normal. The results strongly suggest that gsp mutation is absent in affected and normal tissues in this patient and that the association of hyperparathyroidism and fibrous dysplasia may not represent a variant of the McCune-Albright syndrome.