MOLECULAR-GENETICS OF ANDROGEN INSENSITIVITY SYNDROMES

The androgen receptor belongs to the family of nuclear receptors and c ontains three functional domains: a carboxy-terminal hormone binding r egion, a central cystein rich DNA binding region and an amino-terminal region involved in the expression of androgen regulated genes. Clonin g of the complementary DNA encoding the androgen receptor enabled the characterization of the molecular defects associated with androgen ins ensitivity syndromes, X-linked disorders resulting from androgen actio n defects in target cells. Moreover, androgen receptor gene alteration s have been recently described in two unrelated diseases: male breast cancer and spinal and bulbar muscular atrophy. Our group have identifi ed 16 androgen receptor gene alterations in patients with androgen ins ensitivity syndrome, an amino acid substitution in a patient with a pa rtial androgen insensitivity syndrome and a breast cancer. In 2 famili es, the molecular diagnosis of spinal and bulbar muscular atrophy has been performed.