An activating Gsα mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome

Andrew Shenker, Lee S. Weinstein, Donald E. Sweet, Allen M. Spiegel

Research output: Contribution to journalArticlepeer-review

226 Scopus citations


McCune-Albright syndrome (MAS) is a sporadic disease characterized by polyostotic fibrous dysplasia, cafe′-au-lait spots, and multiple endocrinopathies. The etiology of fibrous dysplasia is unknown. Activating mutations of codon 201 in the gene encoding the α-subunit of G8, the G-protein that stimulates adenylyl cyclase, have been found in all affected MAS tissues that have been studied. Initial attempts to amplify DNA from decalcified paraffin-embedded bone specimens from MAS patients were unsuccessful. Therefore, we analyzed DNA from frozen surgical bone specimens from five MAS patients using polymerase chain reaction and allele-specific oligonucleotide hybridization. Most of the cells in four specimens of dysplastic bone contained a heterozygous mutation encoding substitution of Arg201 of G8α with His, but the mutation was barely detectable in peripheral blood specimens from the patients. Only a small amount of mutant allele was detected in a specimen of normal cortical bone from the fifth patient, although this patient had a high proportion of mutation in other, affected tissues. The mosaic distribution of mutant alleles is consistent with an embryological somatic cell mutation of the G8α gene in MAS. The presence of an activating mutation of G8α in osteoblastic progenitor cells may cause them to exhibit increased proliferation and abnormal differentiation, thereby producing the lesions of fibrous dysplasia.

Original languageEnglish (US)
Pages (from-to)750-755
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Issue number3
StatePublished - Sep 1994
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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