Résumé
McCune-Albright syndrome (MAS) is a rare disorder characterized by the association of precocious puberty (mostly in girls), polyostotic fibrous dysplasia and café-au-lait pigmented skin lesions. In addition to this classical triad, several endocrine disorders, all due to autonomous hormonal hyperproduction, can also be associated, such as pituitary adenomas secreting growth hormone, hyperthyroid goiters, or adrenal hyperplasia. The distribution pattern of skin lesions and the sporadic character of MAS have led to the hypothesis that this syndrome is due to a dominant somatic mutation early in the course of development. Furthermore, the diverse endocrine hyperactivity syndromes observed in MAS have in common the involvement of cells that respond to extracellular signaling by activating the adenyl cyclase system. The identification of somatic mutations of the Gsalpha gene have shown that MAS is due to a post-zygotic activating mutation of the Gsalpha subunit leading to a mosaic distribution of cells bearing constitutively active adenyl cyclase activity. In all patients reported to date, the mutation is a substitution of the arginine residue at position 201 most often into histidine or cysteine. We present here some of the results we have obtained in studying 80 patients presenting one or several signs of MCA for identification of the Arg201 mutation. We used a PCR-based method that allows selective enrichment of mutated DNA. This study, and data in the literature during the last decade, has widened the definition of MAS. Affections as clinically different as somatotropic or thyrotropic adenomas, isolated polyostotic fibrous dysplasia, isolated peripheral precocious puberty and the classic McCune-Albright syndrome all appear to be elements of a wide spectrum of disease based on the same molecular defect. The developmental moment at which the mutation occurs determines both the number of tissues affected and the severity of expression. The application of tools from molecular genetics to the study of this syndrome confirms their essential contribution to a deeper understanding of endocrine pathologies.McCune-Albright syndrome (MAS) is a rare disorder characterized by the association of precocious puberty (mostly in girls), polyostotic fibrous dysplasia and café-au-lait pigmented skin lesions. In addition to this classical triad, several endocrine disorders, all due to autonomous hormonal hyperproduction, can also be associated, such as pituitary adenomas secreting growth hormone, hyperthyroid goiters, or adrenal hyperplasia. The distribution pattern of skin lesions and the sporadic character of MAS have led to the hypothesis that this syndrome is due to a dominant somatic mutation early in the course of development. Furthermore, the diverse endocrine hyperactivity syndromes observed in MAS have in common the involvement of cells that respond to extracellular signaling by activating the adenyl cyclase system. The identification of somatic mutations of the Gsalpha gene have shown that MAS is due to a post-zygotic activating mutation of the Gsalpha subunit leading to a mosaic distribution of cells bearing constitutively active adenyl cyclase activity. In all patients reported to date, the mutation is a substitution of the arginine residue at position 201 most often into histidine or cysteine. We present here some of the results we have obtained in studying 80 patients presenting one or several signs of MCA for identification of the Arg201 mutation. We used a PCR-based method that allows selective enrichment of mutated DNA. This study, and data in the literature during the last decade, has widened the definition of MAS. Affections as clinically different as somatotropic or thyrotropic adenomas, isolated polyostotic fibrous dysplasia, isolated peripheral precocious puberty and the classic McCune-Albright syndrome all appear to be elements of a wide spectrum of disease based on the same molecular defect. The developmental moment at which the mutation occurs determines both the number of tissues affected and the severity of expression. The application of tools from molecular genetics to the study of this syndrome confirms their essential contribution to a deeper understanding of endocrine pathologies.