title: Familial glucocorticoid deficiency: New genes and mechanisms.
abstract: Familial Glucocorticoid deficiency (FGD), in which the adrenal cortex fails to produce glucocorticoids, was first shown to be caused by defects in the receptor for ACTH (MC2R) or its accessory protein (MRAP). Certain mutations in the steroidogenic acute regulatory protein (STAR) can also masquerade as FGD. Recently mutations in mini chromosome maintenance-deficient 4 homologue (MCM4) and nicotinamide nucleotide transhydrogenase (NNT), genes involved in DNA replication and antioxidant defence respectively, have been recognised in FGD cohorts. These latest findings expand the spectrum of pathogenetic mechanisms causing adrenal disease and imply that the adrenal may be hypersensitive to replicative and oxidative stresses. Over time patients with MCM4 or NNT mutations may develop other organ pathologies related to their impaired gene functions and will therefore need careful monitoring.
authors.affiliation: Queen Mary University of London, Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK.
authors.forename: Eirini
authors.initials: E
authors.lastname: Meimaridou
authors.forename: Claire R
authors.initials: CR
authors.lastname: Hughes
authors.forename: Julia
authors.initials: J
authors.lastname: Kowalczyk
authors.forename: Leonardo
authors.initials: L
authors.lastname: Guasti
authors.forename: J Paul
authors.initials: JP
authors.lastname: Chapple
authors.forename: Peter J
authors.initials: PJ
authors.lastname: King
authors.forename: Li F
authors.initials: LF
authors.lastname: Chan
authors.forename: Adrian J L
authors.initials: AJ
authors.lastname: Clark
authors.forename: Louise A
authors.initials: LA
authors.lastname: Metherell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000307:Adrenal Gland Diseases / Q000235:genetics*; D000311:Adrenal Glands / Q000378:metabolism*; D000309:Adrenal Insufficiency / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005938:Glucocorticoids / Q000096:biosynthesis*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D064148:Minichromosome Maintenance Complex Component 4; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D061087:NADP Transhydrogenase, AB-Specific / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics / Q000378:metabolism; D043202:Steroid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; C458099:MRAP protein, human; C551627:MRAP2 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D044103:Receptor, Melanocortin, Type 2; D000098682:Steroidogenic Acute Regulatory Protein; D002786:Cholesterol Side-Chain Cleavage Enzyme; D061087:NADP Transhydrogenase, AB-Specific; C556045:NNT protein, human; C099243:MCM4 protein, human; D064148:Minichromosome Maintenance Complex Component 4