{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:35:33Z","timestamp":1759336533886},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T00:00:00Z","timestamp":1264982400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.bioscientifica.com\/journals\/reuselicenceeje\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin\u2013angiotensin\u2013aldosterone axis have been reported in a subset of patients at presentation. Anecdotally, some patients with FGD have been initially diagnosed as having Addison's disease (AD), with implications for treatment and genetic counselling. Currently, mutations in three genes: the ACTH receptor (<jats:italic>MC2R<\/jats:italic>); the melanocortin 2 receptor accessory protein (<jats:italic>MRAP<\/jats:italic>); and the steroidogenic acute regulatory protein (<jats:italic>STAR<\/jats:italic>) are known to give rise to FGD types 1\u20133. We investigated a cohort of autoantibody-negative AD patients for mutations in these genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty patients with known AD without evidence of autoimmune disease were screened for mutations in <jats:italic>MC2R<\/jats:italic>, <jats:italic>MRAP<\/jats:italic> and <jats:italic>STAR<\/jats:italic>. In addition, patients were genotyped for the <jats:italic>MC2R<\/jats:italic> promoter polymorphism previously associated with reduced responsiveness to ACTH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No mutations in <jats:italic>MC2R<\/jats:italic>, <jats:italic>MRAP<\/jats:italic> or <jats:italic>STAR<\/jats:italic> were identified in any patient. The frequencies of the <jats:italic>MC2R<\/jats:italic> promoter polymorphism were similar to those reported in healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FGD does not appear to be underdiagnosed in the AD population. However, in \u223c50% of patients with FGD, no genetic cause has yet been identified and it is possible that the other, as yet unidentified, genes giving rise to FGD may be implicated in AD.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-09-0720","type":"journal-article","created":{"date-parts":[[2009,11,11]],"date-time":"2009-11-11T04:25:33Z","timestamp":1257913533000},"page":"357-359","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":6,"title":["Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency"],"prefix":"10.1093","volume":"162","author":[{"given":"R P","family":"Dias","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L F","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L A","family":"Metherell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S H S","family":"Pearce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A J L","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/162\/2\/357.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/162\/2\/357.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:24:08Z","timestamp":1676391848000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/162\/2\/357\/6676563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-09-0720","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,2]]}}}