STUDIES ON MCCUNE-ALBRIGHT SYNDROME

Project: Research project

Project Details

Description

McCune-Albright syndrome (MAS) is a non-genetic disorder in which affected
subjects show a variety of seemingly unrelated abnormalities including
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 has been completely
enigmatic, but speculations have 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 subset-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. 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

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases

ASJC

  • Genetics(clinical)

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