{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:40:37Z","timestamp":1791092437377,"version":"4.1.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,8,18]]},"abstract":"<jats:p>\n                    Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (\n                    <jats:italic>HSD11B2<\/jats:italic>\n                    ) encoding the 11\u03b2-hydroxysteroid dehydrogenase type 2 enzyme (11\u03b2-HSD2) cause AME. Typical patients with AME have defective 11\u03b2-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-\n                    <jats:sup>3<\/jats:sup>\n                    H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the\n                    <jats:italic>HSD11B2<\/jats:italic>\n                    gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0\u20136% in typical patients with AME whereas the normal conversion is 90\u201395%. Molecular analysis of the\n                    <jats:italic>HSD11B2<\/jats:italic>\n                    gene of this patient showed a homozygous C\u2192T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation.\n                    <jats:italic>In vitro<\/jats:italic>\n                    expression studies showed an increase in the\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>m<\/jats:sub>\n                    (300 nM) over normal (54 nM). Because \u224840% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the\n                    <jats:italic>HSD11B2<\/jats:italic>\n                    gene.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.17.10200","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"10200-10205","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":115,"title":["A genetic defect resulting in mild low-renin hypertension"],"prefix":"10.1073","volume":"95","author":[{"given":"Robert C.","family":"Wilson","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Dave-Sharma","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Qing","family":"Wei","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varuni R.","family":"Obeyesekere","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Li","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zygmunt S.","family":"Krozowski","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric H. L.","family":"Shackleton","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Bradlow","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Wiens","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. Box 348 Prahran, Melbourne, Australia 3181; Division of Nephrology, Inselspital 3010 Bern, Switzerland; Mass Spectrometry Facility, Children\u2019s Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809; and Wichita Clinic, Bethel Office, 201 South Pine Street, Newton, KS 67114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"New","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, The New York Hospital\u2013Cornell Medical Center, 525 East 68th Street, New York, NY 10021; Laboratory of Molecular Hypertension, Baker Medical Research Institute, P.O. 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