Activating mutation of GS alpha in McCune-Albright syndrome causes skin pigmentation by tyrosinase gene activation on affected melanocytes

Horm Res. 1999;52(5):235-40. doi: 10.1159/000023467.

Abstract

McCune-Albright syndrome (MAS) is a sporadic disease characterized by café-au-lait spots, polyostotic fibrous dysplasia and hyperfunctional endocrinopathies. To elucidate the mechanism of skin pigmentation, melanocytes, keratinocytes and fibroblasts were primary cultured from the café-au-lait spot of a MAS patient. Then, mutational analysis and morphologic evaluation were performed. Also, cAMP level and tyrosinase gene expression in cultured cells were determined. Only Gsalpha mutation was found in affected melanocytes and the cAMP level in affected melanocytes was higher than that of normal melanocytes. The mRNA expression of tyrosinase gene was increased in the affected melanocytes. This study suggests that skin pigmentation of MAS results from activating mutation of Gsalpha in melanocytes and the mechanism involves the c-AMP-mediated tyrosinase gene activation.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • Child
  • Cyclic AMP / metabolism
  • DNA Primers / genetics
  • Female
  • Fibrous Dysplasia, Polyostotic / enzymology*
  • Fibrous Dysplasia, Polyostotic / genetics*
  • Fibrous Dysplasia, Polyostotic / pathology
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Melanocytes / enzymology*
  • Melanocytes / pathology
  • Monophenol Monooxygenase / genetics*
  • Mutation*
  • Skin Pigmentation / genetics*
  • Skin Pigmentation / physiology
  • Transcriptional Activation

Substances

  • DNA Primers
  • Cyclic AMP
  • Monophenol Monooxygenase
  • GTP-Binding Protein alpha Subunits, Gs