Project: Research project

Project Details


McCune-Albright syndrome (MAS) is a non-inherited disorder in which
affected subjects show a variety of seemingly unrelated abnormalities
include the classic triad of polyostotic fibrous dysplasia, pigmented
skin lesions (cafe-au-lait spots), and autonomous hyperfunction of
various endocrine organs including gonads, anterior pituitary, thyroid,
and adrenal cortex. The endocrine abnormalities lead to precocious
puberty, gigantism, hyperthyroidism, and hypercortisolism. The cause of
this sporadic disorder had been completely enigmatic, with speculations
centered on a defect in signal transduction leading to endocrine
hyperfunction. The distribution of skin lesions has also suggested the
possibility of a somatic mutation acquired early in embryogenesis and
affecting only a subunit of cells (mosaicism). Since a G protein
mutation could plausibly explain the endocrine manifestations, we
searched for and found mutations of the Gs-alpha gene that lead to
constitutive activation of the Gs protein. These mutations were found
in a mosaic distribution; notably, mutant gene was undetectable in
normal-appearing portions of endocrine glands, but was present at
heterozygous levels in neoplastic portions of endocrine tissue. Mutant
Gs-alpha was also detected in dysplastic bone lesions. Occurrence of
mutant Gs-alpha in organs such as heart and liver suggest a possible role
in "non-classical" manifestations, including sudden death. Our studies
suggest that MAS is caused by a somatic mutation in the Gs-alpha gene
occurring early in development and found in a mosaic distribution.
StatusNot started


  • Endocrinology, Diabetes and Metabolism


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