{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:55:04Z","timestamp":1791831304262,"version":"4.3.4"},"reference-count":23,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,1]]},"abstract":"<jats:p>Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and\/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases.<\/jats:p>\n                  <jats:p>Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified.<\/jats:p>\n                  <jats:p>Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection.<\/jats:p>\n                  <jats:p>Setting: The study was conducted at secondary and tertiary referral centers.<\/jats:p>\n                  <jats:p>Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study.<\/jats:p>\n                  <jats:p>Interventions: There were no interventions.<\/jats:p>\n                  <jats:p>Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families.<\/jats:p>\n                  <jats:p>Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD.<\/jats:p>\n                  <jats:p>Partial loss-of-function mutations in StAR can present with glucocorticoid deficiency alone; genetic diagnosis in familial glucocorticoid deficiency is therefore important for correct replacement therapy and genetic counseling.<\/jats:p>","DOI":"10.1210\/jc.2009-0467","type":"journal-article","created":{"date-parts":[[2009,9,22]],"date-time":"2009-09-22T21:55:08Z","timestamp":1253656508000},"page":"3865-3871","source":"Crossref","is-referenced-by-count":137,"title":["Nonclassic Lipoid Congenital Adrenal Hyperplasia Masquerading as Familial Glucocorticoid Deficiency"],"prefix":"10.1210","volume":"94","author":[{"given":"Louise A.","family":"Metherell","sequence":"first","affiliation":[{"name":"Centre for Endocrinology (L.A.M., A.J.L.C.), Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine, London EC1M 6BQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Naville","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 855 (D.N., M.B.), Lyon F-69008, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Halaby","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (G.H.), Saint-Joseph University, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Begeot","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 855 (D.N., M.B.), Lyon F-69008, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Huebner","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital (A.H.), Technical University Dresden, 01187 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Nu\u0308rnberg","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics and Institute for Genetics (P.N., G.N.), University of Cologne, D-50674 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nu\u0308rnberg","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (G.H.), Saint-Joseph University, Beirut, Lebanon"},{"name":"Cologne Center for Genomics and Institute for Genetics (P.N., G.N.), University of Cologne, D-50674 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Green","sequence":"additional","affiliation":[{"name":"Discipline of Genetics (J.G.), Faculty of Medicine, Memorial Hospital, St. John\u2019s, NL Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy W.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Diabetes, and Metabolism (J.W.T., N.P.K., W.A.), School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils P.","family":"Krone","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Diabetes, and Metabolism (J.W.T., N.P.K., W.A.), School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Unit (L.L., J.C.A.), Developmental Endocrinology Research Group, UCL Institute of Child Health, University College London, London WC1E 6BT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Racine","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology (M.R.), Helen DeVos Children\u2019s Hospital, Grand Rapids, Michigan 49503"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan M.","family":"Berney","sequence":"additional","affiliation":[{"name":"The Orchid Tissue Laboratory, Institute of Cancer (D.M.B.), William Harvey Research Institute, Barts and the London School of Medicine, London EC1M 6BQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Achermann","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Unit (L.L., J.C.A.), Developmental Endocrinology Research Group, UCL Institute of Child Health, University College London, London WC1E 6BT, United 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