{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:40:41Z","timestamp":1791398441945,"version":"4.3.3"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3]]},"abstract":"\nObjective<\/jats:title>\nCYP11A1<\/jats:italic> mutations cause P450 side-chain cleavage (scc) deficiency, a rare form of congenital adrenal hyperplasia with a wide clinical spectrum. We detail the phenotype and evolution in a male sibship identified by HaloPlex targeted capture array.<\/jats:p>\n<\/jats:sec>\n\nFamily study<\/jats:title>\nThe youngest of three brothers from a non-consanguineous Scottish family presented with hyperpigmentation at 3.7 years. Investigation showed grossly impaired glucocorticoid function with ACTH elevation, moderately impaired mineralocorticoid function, and normal external genitalia. The older brothers were found to be pigmented also, with glucocorticoid impairment but normal electrolytes. Linkage studies in 2002 showed that all three brothers had inherited the same critical regions of the maternal X chromosome suggesting an X-linked disorder, but analysis of NR0B1<\/jats:italic> (DAX-1, adrenal hypoplasia) and ABCD1<\/jats:italic> (adrenoleukodystrophy) were negative.<\/jats:p>\nIn 2016, next-generation sequencing revealed compound heterozygosity for the rs6161 variant in CYP11A1<\/jats:italic> (c.940G>A, p.Glu314Lys), together with a severely disruptive frameshift mutation (c.790_802del, K264Lfs*5). The brothers were stable on hydrocortisone and fludrocortisone replacement, testicular volumes (15\u201320 mL), and serum testosterone levels (24.7, 33.3, and 27.2 nmol\/L) were normal, but FSH (41.2 \u00b5\/L) was elevated in the proband. The latter had undergone left orchidectomy for suspected malignancy at the age of 25 years and was attending a fertility clinic for oligospermia. Initial histology was reported as showing nodular Leydig cell hyperplasia. However, histological review using CD56 staining confirmed testicular adrenal rest cell tumour (TART).<\/jats:p>\n<\/jats:sec>\n\nConclusion<\/jats:title>\nThis kinship with partial P450scc deficiency demonstrates the importance of precise diagnosis in primary adrenal insufficiency to ensure appropriate counselling and management, particularly of TART.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-19-0696","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T16:33:01Z","timestamp":1580142781000},"page":"K15-K24","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":22,"title":["Long-term outcome of partial P450 side-chain cleavage enzyme deficiency in three brothers: the importance of early diagnosis"],"prefix":"10.1093","volume":"182","author":[{"given":"Wafa","family":"Kallali","sequence":"first","affiliation":[{"name":"1Children\u2019s Hospital El Bechir Hamza of Tunis, Tunis, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewan","family":"Gray","sequence":"additional","affiliation":[{"name":"2David Elder Medical Practice, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Zain","family":"Mehdi","sequence":"additional","affiliation":[{"name":"3Pathology Department, Glan Clwyd Hospital, Rhyl, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lindsay","sequence":"additional","affiliation":[{"name":"4Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A","family":"Metherell","sequence":"additional","affiliation":[{"name":"5Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Buonocore","sequence":"additional","affiliation":[{"name":"6Genetics & Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenifer P","family":"Suntharalingham","sequence":"additional","affiliation":[{"name":"6Genetics & Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Achermann","sequence":"additional","affiliation":[{"name":"6Genetics & Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Donaldson","sequence":"additional","affiliation":[{"name":"7Child Health Section of University of Glasgow School of Medicine, Queen Elizabeth University Hospital, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/182\/3\/EJE-19-0696.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/182\/3\/EJE-19-0696.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:13:56Z","timestamp":1676391236000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/182\/3\/K15\/6653936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/eje-19-0696","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3]]}}}