title: The genetics of ACTH resistance syndromes.
abstract: Inherited adrenocorticotropin (ACTH) resistance diseases are rare and include triple A syndrome and familial glucocorticoid deficiency (FGD). These conditions show genetic heterogeneity, i.e., the identical clinical phenotype may result from defects in more than one gene. Clinically, FGD is characterized only by ACTH resistance, while the triple A syndrome exhibits a variety of additional clinical features. FGD is caused by mutations in the ACTH receptor (melanocortin 2 receptor, MC2R) and the recently identified melanocortin 2 receptor accessory protein (MRAP) genes. In addition, linkage to a locus on chromosome 8 has been demonstrated. The identification of further genes in ACTH resistance syndromes may reveal novel aspects of MC2R signalling and trafficking. This review will summarize the clinical, biochemical and genetic aspects of these rare but informative diseases.
authors.affiliation: Centre for Endocrinology, William Harvey Research Institute, Queen Mary's School of Medicine and Dentistry at Barts & The London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK. l.a.metherell@qmul.ac.uk
authors.forename: Louise A
authors.initials: LA
authors.lastname: Metherell
authors.forename: Li F
authors.initials: LF
authors.lastname: Chan
authors.forename: Adrian J L
authors.initials: AJ
authors.lastname: Clark
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D004351:Drug Resistance / Q000235:genetics*; D005938:Glucocorticoids / Q000172:deficiency*; D020249:Hormone Replacement Therapy; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics; D043202:Steroid Metabolism, Inborn Errors / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D013577:Syndrome
chemical_list: C416506:AAAS protein, human; D005938:Glucocorticoids; C458099:MRAP protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D044103:Receptor, Melanocortin, Type 2; D000324:Adrenocorticotropic Hormone