{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T12:36:48Z","timestamp":1771591008966,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000382","name":"Society for Endocrinology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["IEF\u2010GA\u20102009\u2010255424"],"award-info":[{"award-number":["IEF\u2010GA\u20102009\u2010255424"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Steroid 11\u03b2\u2010hydroxylase (<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B1) deficiency (11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content>) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content> appears to be a rare condition. Our study assessed the residual <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B1 function of detected mutations, adding to the spectrum of mild 11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content>, and illustrates the variability of the clinical presentation of 11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>Five patients presented with mild to moderate 11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content>. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,<jats:styled-content style=\"fixed-case\">XX<\/jats:styled-content> female patient was diagnosed with virilization of the external genitalia 2\u00a0years after birth. Direct <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing was carried out to perform <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B1<\/jats:italic> mutation analysis. The <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B1<\/jats:italic> mutations were functionally characterized using an <jats:italic>in\u00a0vitro<\/jats:italic> expression system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B1<\/jats:italic>\u2010inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B1 enzymatic activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mutations causing partial impairment of 11\u03b2\u2010hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content>, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content> can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11<jats:styled-content style=\"fixed-case\">OHD<\/jats:styled-content> and consequently initiation of personalized treatment is essential to prevent co\u2010morbidities caused by androgen excess and hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12834","type":"journal-article","created":{"date-parts":[[2015,6,6]],"date-time":"2015-06-06T15:02:56Z","timestamp":1433602976000},"page":"629-635","source":"Crossref","is-referenced-by-count":31,"title":["Characterization of the molecular genetic pathology in patients with 11\u03b2\u2010hydroxylase deficiency"],"prefix":"10.1111","volume":"83","author":[{"given":"Christiaan F.","family":"Mooij","sequence":"first","affiliation":[{"name":"Centre for Endocrinology, Diabetes, and Metabolism School of Clinical and Experimental Medicine University of Birmingham Birmingham UK"},{"name":"Department of Pediatric Endocrinology Amalia Children's Hospital Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Parajes","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Diabetes, and Metabolism School of Clinical and Experimental Medicine University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian T.","family":"Rose","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Diabetes, and Metabolism School of Clinical and Experimental Medicine University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela E.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Diabetes, and Metabolism School of Clinical and Experimental Medicine University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taner","family":"Bayraktaroglu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Department of Internal Medicine Bulent Ecev\u0131t University Zonguldak Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.H.","family":"Wass","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Oxford Centre for Diabetes, Endocrinology and Metabolism Churchill Hospital Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.C.","family":"Connell","sequence":"additional","affiliation":[{"name":"School of Medicine Ninewells Hospital and Medical School University of Dundee Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Ray","sequence":"additional","affiliation":[{"name":"Endocrine Sciences Research Group University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Arlt","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Diabetes, and Metabolism School of Clinical and 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