{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:52:59Z","timestamp":1790553179350,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1996,6]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            The syndrome of apparent mineralocorticoid excess is a form of hypertension inherited in an autosomal recessive manner. This disorder results from mutations in the\n            <jats:italic>HSD11K<\/jats:italic>\n            (\n            <jats:italic>HSD11B2<\/jats:italic>\n            ) gene, which encodes the kidney isozyme of 11\u03b2-hydroxysteroid dehydrogenase. This enzyme converts active glucocorticoids such as cortisol and corticosterone to their inactive metabolites cortisone and 11-dehydrocorticosterone. An elevated ratio of cortisol to cortisone metabolites in the urine (tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone [(THF+aTHF)\/THE]) is considered pathognomic for this disorder. To determine whether the biochemical phenotype of this disorder is correlated with genotype, we expressed enzymes carrying each of the six known missense mutations in cultured cells. Only one mutant, R337C, had detectable activity in cell lysates, but five of six mutants were partially active in whole cells. Apparent kinetic constants for cortisol and corticosterone were determined in whole cells, and the apparent first-order rate constant,\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            \/\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>m<\/jats:sub>\n            , was used as a measure of enzymatic activity. The urinary (THF+aTHF)\/THE ratio in patients carrying each mutation was strongly correlated with in vitro enzymatic activity of the corresponding mutant (\n            <jats:italic>r<\/jats:italic>\n            =.839,\n            <jats:italic>P<\/jats:italic>\n            =.001 with cortisol as the substrate). We conclude that the biochemical phenotype of the syndrome of apparent mineralocorticoid excess is largely determined by genotype.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.27.6.1193","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"1193-1199","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Apparent Mineralocorticoid Excess"],"prefix":"10.1161","volume":"27","author":[{"given":"Tomoatsu","family":"Mune","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrin C.","family":"White","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-49-5-757"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47248-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend-4-12-1827"},{"key":"e_1_3_2_4_2","first-page":"687","volume":"77","year":"1993","unstructured":"Nikkila H, Tannin GM, New MI, Taylor NF, Kalaitzoglou G, Monder C, White PC. Defects in the HSD11 gene encoding 11 beta-hydroxysteroid dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11-oxoreductase deficiency. J Clin Endocrinol Metab. 1993;77:687-691.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90030-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47142-6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1231"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-394"},{"key":"e_1_3_2_9_2","first-page":"2263","volume":"80","year":"1995","unstructured":"Wilson RC, Krozowski ZS, Li K, Obeyesekere VR, Razzaghy-Azar M, Harbison MD, Wei JQ, Shackleton CH, Funder JW, New MI. A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1995;80:2263-2266.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_10_2","first-page":"3145","volume":"80","year":"1995","unstructured":"Wilson RC, Harbison MD, Krozowski ZS, Funder JW, Shackleton CH, Hanauske-Abel HM, Wei JQ, Hertecant J, Moran A, Neiberger RE, Balfe JW, Fattah A, Daneman D, Licholai T, New MI. Several homozygous mutations in the gene for 11\u03b2-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1995;80:3145-3150.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3037703"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2845584"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)90742-8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)71614-1"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","unstructured":"Higuchi R. Recombinant PCR. In: Innis MA Gelfand DH Sninsky JJ White TJ eds. PCR Protocols. San Diego Calif: Academic Press; 1990:177-183.","DOI":"10.1016\/B978-0-12-372180-8.50026-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.1.85"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90030-2"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(08)60447-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.22.10064"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)92373-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(93)90003-9"},{"key":"e_1_3_2_22_2","first-page":"3381","volume":"80","year":"1995","unstructured":"Obeyesekere VR, Ferrari P, Andrews RK, Wilson RC, New MI, Funder JW, Krozowski ZS. The R337C mutation generates a high Km 11\u03b2-hydroxysteroid dehydrogenase type II enzyme in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1995;80:3381-3383.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)45304-X"},{"key":"e_1_3_2_24_2","first-page":"716","volume":"7","year":"1993","unstructured":"Simard J, Rheaume E, Sanchez R, Laflamme N, de Launoit Y, Luu-The V, van Seters AP, Gordon RD, Bettendorf M, Heinrich U, Moshang T, New MI, Labrie F. Molecular basis of congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency. Mol Endocrinol. 1993;7:716-728.","journal-title":"Mol Endocrinol"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115897"},{"key":"e_1_3_2_26_2","first-page":"1318","volume":"6","year":"1992","unstructured":"Helmberg A, Tusie-Luna MT, Tabarelli M, Kofler R, White PC. R339H and P453S: CYP21 mutations associated with nonclassic steroid 21-hydroxylase deficiency that are not apparent gene conversions. Mol Endocrinol. 1992;6:1318-1322.","journal-title":"Mol Endocrinol"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-5-685"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)55351-5"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.27.6.1193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T17:08:40Z","timestamp":1715533720000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.27.6.1193"}},"subtitle":["Genotype Is Correlated With Biochemical Phenotype"],"short-title":[],"issued":{"date-parts":[[1996,6]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1996,6]]}},"alternative-id":["10.1161\/01.HYP.27.6.1193"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.27.6.1193","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,6]]},"assertion":[{"value":"1996-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-03-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}