{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T20:09:46Z","timestamp":1782677386455,"version":"3.54.5"},"reference-count":13,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Liddle\u2019s syndrome is an autosomal dominant form of hypertension that resembles primary hyperaldosteronism, is characterized by the early onset of hypertension with hypokalemia and suppression of both PRA and aldosterone, and is caused by mutations in the carboxyl-terminus of the\u03b2 - or \u03b3-subunits of the renal epithelial sodium channel. We describe a kindred (K176) whose distinguishing clinical features were mild hypertension and decreased aldosterone secretion. The index case was a 16-yr-old girl with intermittent mild hypertension and hypokalemia and subnormal PRA, aldosterone, 18-hydroxycorticosterone, and deoxycortisol levels, but normal cortisol\/cortisone metabolite ratio and cortisol half-life. A frameshift mutation in the carboxyl-terminus of the \u03b2-subunit of the epithelial sodium channel was identified in the index case, establishing the diagnosis of Liddle\u2019s syndrome. Sixteen at-risk relatives of the index case were tested. Seven new subjects were heterozygous for the mutation found in the index case, and two deceased obligate carriers were identified. All genetically affected adult subjects had a history of mild hypertension, and four had a history of hypokalemia. Basal and postcosyntropin plasma aldosterone and urinary aldosterone levels were significantly suppressed in those positive for the mutation. The family demonstrates variability in the severity of hypertension and hypokalemia in this disease, raising the possibility that this disease may be underdiagnosed among patients with essential hypertension.<\/jats:p>","DOI":"10.1210\/jcem.82.4.3862","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:48Z","timestamp":1389200508000},"page":"1071-1074","source":"Crossref","is-referenced-by-count":3,"title":["Liddle\u2019s Syndrome: Prospective Genetic Screening and Suppressed Aldosterone Secretion in an Extended Kindred*"],"prefix":"10.1210","volume":"82","author":[{"given":"James W.","family":"Findling","sequence":"first","affiliation":[{"name":"Endocrine Research Laboratory, Department of Medicine, St. Luke\u2019s Medical Center, Medical College of Wisconsin (J.W.F., H.R.), Milwaukee, Wisconsin 53215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hershel","family":"Raff","sequence":"additional","affiliation":[{"name":"Endocrine Research Laboratory, Department of Medicine, St. Luke\u2019s Medical Center, Medical College of Wisconsin (J.W.F., H.R.), Milwaukee, Wisconsin 53215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni H.","family":"Hansson","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Departments of Medicine and Genetics, Boyer Center for Molecular Medicine, Yale University School of Medicine (J.H.H., R.P.L.), New Haven, Connecticut 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Lifton","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Departments of Medicine and Genetics, Boyer Center for Molecular Medicine, Yale University School of Medicine (J.H.H., R.P.L.), New Haven, Connecticut 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071622171640700_R1","first-page":"199","article-title":"A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion.","volume":"76","author":"Liddle","year":"1963","journal-title":"Trans Assoc Am Physicians"},{"key":"2020071622171640700_R2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1056\/NEJM199401203300305","article-title":"Brief report: Liddle\u2019s syndrome revisited.","volume":"330","author":"Botero-Velez","year":"1994","journal-title":"N Engl J Med"},{"key":"2020071622171640700_R3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0092-8674(94)90250-X","article-title":"Liddle\u2019s syndrome: heritable human hypertension caused by mutations in the \u03b2 subunit of the epithelial sodium channel.","volume":"79","author":"Shimkets","year":"1994","journal-title":"Cell"},{"key":"2020071622171640700_R4","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/ng0995-76","article-title":"Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle\u2019s syndrome.","volume":"11","author":"Hansson","year":"1995","journal-title":"Nat Genet"},{"key":"2020071622171640700_R5","doi-asserted-by":"crossref","first-page":"11495","DOI":"10.1073\/pnas.92.25.11495","article-title":"A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle\u2019s syndrome and identifies a proline-rich segment of the protein critical for regulation of channel activity.","volume":"92","author":"Hansson","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071622171640700_R6","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1172\/JCI118606","article-title":"Liddle\u2019s disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene.","volume":"97","author":"Tamura","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071622171640700_R7","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1073\/pnas.92.12.5699","article-title":"A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in Xenopus laevis oocyte expression system.","volume":"92","author":"Schild","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071622171640700_R8","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/0092-8674(95)90212-0","article-title":"Mechanism by which Liddle\u2019s syndrome mutations increase activity of human epithelia Na+ channel.","volume":"83","author":"Snyder","year":"1995","journal-title":"Cell"},{"key":"2020071622171640700_R9","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1002\/j.1460-2075.1996.tb00594.x","article-title":"Identification of a PY motif in the epithelial sodium channel subunits as a target sequence for mutations causing channel activation found in Liddle\u2019s syndrome.","volume":"15","author":"Schild","year":"1996","journal-title":"EMBO J"},{"key":"2020071622171640700_R10","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S0022-3476(05)80382-8","article-title":"Blood pressure nomograms for children and adolescents, by height, sex, and age, in the United States.","volume":"123","author":"Rosner","year":"1993","journal-title":"J Pediatr"},{"key":"2020071622171640700_R11","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1126\/science.272.5262.676","article-title":"Molecular genetics of human blood pressure variation.","volume":"272","year":"1996","journal-title":"Science"},{"key":"2020071622171640700_R12","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1002\/j.1460-2075.1996.tb00593.x","article-title":"WW domains of Nedd4 bind to proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle\u2019s syndrome.","volume":"15","author":"Staub","year":"1996","journal-title":"EMBO J"},{"key":"2020071622171640700_R13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/00004872-199501000-00005","article-title":"Plasma renin methodology: inadequate sensitivity and accuracy of direct renin assay for clinical applications compared with the traditional enzymatic plasma renin activity assay.","volume":"13","author":"Sealey","year":"1995","journal-title":"J Hypertension"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/82\/4\/1071\/13124746\/jcem1071.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/82\/4\/1071\/13124746\/jcem1071.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T10:36:30Z","timestamp":1594982190000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/82\/4\/1071\/2866195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,4,1]]},"references-count":13,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1997,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jcem.82.4.3862","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,4,1]]}}}