{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:38:35Z","timestamp":1791923915367,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T00:00:00Z","timestamp":1442966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:label\/><jats:p>Aldosterone\u2010producing adenomas (<jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content>s) and bilateral adrenal hyperplasia are important causes of secondary hypertension. Somatic mutations in <jats:italic>KCNJ5<\/jats:italic>,<jats:italic> CACNA1D<\/jats:italic>,<jats:italic> ATP1A1<\/jats:italic>,<jats:italic> ATP2B3<\/jats:italic> and <jats:italic>CTNNB1<\/jats:italic> have been described in <jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize clinical\u2013pathological features in <jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content>s and unilateral adrenal hyperplasia, and correlate them with genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Measurements<\/jats:title><jats:p>Clinical and pathological characteristics of 90 APAs and seven diffusely or focally hyperplastic adrenal glands were reviewed, and samples were examined for mutations in known disease genes by Sanger or exome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mutation frequencies were as follows: <jats:italic>KCNJ5<\/jats:italic>, 37\u00b71%; <jats:italic>CACNA1D<\/jats:italic>, 10\u00b73%; <jats:italic>ATP1A1<\/jats:italic>, 8\u00b72%; <jats:italic>ATP2B3<\/jats:italic>, 3\u00b71%; and <jats:italic>CTNNB1<\/jats:italic>, 2\u00b71%. Previously unidentified mutations included I157K, F154C and two insertions (I150_G151insM and I144_E145insAI) in <jats:italic>KCNJ5<\/jats:italic>, all close to the selectivity filter, V426G_V427Q_A428_L433del in <jats:italic>ATP2B3<\/jats:italic> and A39Efs*3 in <jats:italic>CTNNB1<\/jats:italic>. Mutations in <jats:italic>KCNJ5<\/jats:italic> were associated with female and other mutations with male gender (<jats:italic>P<\/jats:italic> = 0\u00b7007). On computed tomography, <jats:italic>KCNJ5<\/jats:italic>\u2010mutant tumours displayed significantly greater diameter (<jats:italic>P<\/jats:italic> = 0\u00b7023), calculated area (<jats:italic>P<\/jats:italic> = 0\u00b7002) and lower precontrast Hounsfield units (<jats:italic>P<\/jats:italic> = 0\u00b70002) <jats:italic>vs<\/jats:italic> tumours with mutations in other genes. Accordingly, <jats:italic>KCNJ5<\/jats:italic>\u2010mutant tumours were predominantly comprised of lipid\u2010rich fasciculata\u2010like clear cells, whereas other tumours were heterogeneous (<jats:italic>P<\/jats:italic> = 5 \u00d7 10<jats:sup>\u22126<\/jats:sup> <jats:italic>vs<\/jats:italic> non\u2010<jats:italic>KCNJ5<\/jats:italic> mutant and <jats:italic>P<\/jats:italic> = 0\u00b70003 <jats:italic>vs<\/jats:italic> wild\u2010type tumours, respectively). <jats:italic>CACNA1D<\/jats:italic> mutations were present in two samples with hyperplasia without adenoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>KCNJ5\u2010<\/jats:italic>mutant tumours appear to be associated with fasciculata\u2010like clear cell predominant histology and tend to be larger with a characteristic imaging phenotype. Novel somatic <jats:italic>KCNJ5<\/jats:italic> variants likely cause adenomas by loss of potassium selectivity, similar to previously described mutations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12873","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T14:20:51Z","timestamp":1438957251000},"page":"779-789","source":"Crossref","is-referenced-by-count":138,"title":["Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype"],"prefix":"10.1111","volume":"83","author":[{"given":"Ute I.","family":"Scholl","sequence":"first","affiliation":[{"name":"Department of Genetics and Howard Hughes Medical Institute Yale University School of Medicine, New Haven CT USA"},{"name":"Department of Nephrology Medical School Heinrich Heine University University Hospital D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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