title: Mutations in the Gs alpha gene causing hormone resistance.
abstract: G-protein-coupled receptors (GPCRs) and G proteins mediate the effects of a number of hormones of relevance to endocrinology. Genes encoding these molecules may be targets of loss- or gain-of-function mutations, resulting in endocrine disorders. The only mutational change of G proteins so far unequivocally associated with endocrine disorders occurs in the Gsalpha gene (GNAS1, guanine nucleotide binding protein alpha stimulating activity polypeptide 1), which activates cyclic AMP (cAMP)-dependent pathways. Heterozygous loss-of-function mutations of GNAS1 in the active maternal allele cause resistance to hormones acting through Gsalpha-coupled GPCRs, whereas somatic gain-of-function mutations cause proliferation of endocrine cells recognizing cAMP as mitogen. This review will focus on inactivating mutations leading to hormone resistance syndromes, i.e., pseudohypoparathyroidism types Ia and Ib.
authors.affiliation: Endocrine Unit, Department of Medical Sciences, University of Milan, Fondazione Ospedale Maggiore, Policlinico, Mangiagalli e Regina Elena IRCCS, Via F. Sforza, 35, 20122 Milan, Italy. giovanna.mantovani@unimi.it
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantovani
authors.forename: Anna
authors.initials: A
authors.lastname: Spada
mesh_terms: D002864:Chromogranins; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D009154:Mutation; D010281:Parathyroid Hormone / Q000494:pharmacology; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D011556:Pseudopseudohypoparathyroidism / Q000235:genetics
chemical_list: D002864:Chromogranins; D010281:Parathyroid Hormone; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs