{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:24:26Z","timestamp":1789741466015,"version":"4.0.1"},"reference-count":37,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:p>The human microsomal 11\u03b2-hydroxysteroid dehydrogenase type 2 (11\u03b2HSD2) metabolizes active cortisol into cortisone and protects the mineralocorticoid receptor from glucocorticoid occupancy. In a congenital deficiency of 11\u03b2-HSD2, the protective mechanism fails and cortisol gains inappropriate access to mineralocorticoid receptor, resulting in low-renin hypertension and hypokalemia. In the present study, we describe the clinical and molecular genetic characterization of a patient with a new mutation in the HSD11B2 gene. This is a 4-yr-old male with arterial hypertension. The plasma renin activity and serum aldosterone were undetectable in the presence of a high cortisol to cortisone ratio. PCR amplification and sequence analysis of HSD11B2 gene showed the homozygous mutation in exon 4 Asp223Asn (GAC\u2192AAC) and a single nucleotide substitution C\u2192T in intron 3. Using site-directed mutagenesis, we generated a mutant 11\u03b2HSD2 cDNA containing the Asp223Asn mutation. Wild-type and mutant cDNA was transfected into Chinese hamster ovary cells and enzymatic activities were measured using radiolabeled cortisol and thin-layer chromatography. The mRNA and 11\u03b2HSD2 protein were detected by RT-PCR and Western blot, respectively. Wild-type and mutant 11\u03b2HSD2 protein was expressed in Chinese hamster ovary cells, but the mutant enzyme had only 6% of wild-type activity. In silico 3D modeling showed that Asp223Asn changed the enzyme\u2019s surface electrostatic potential affecting the cofactor and substrate enzyme-binding capacity. The single substitution C\u2192T in intron 3 (IVS3 + 14 C\u2192T) have been previously reported that alters the normal splicing of pre-mRNA, given a nonfunctional protein. These findings may determine the full inactivation of this enzyme, explaining the biochemical profile and the early onset of hypertension seen in this patient.<\/jats:p>","DOI":"10.1210\/jc.2002-021909","type":"journal-article","created":{"date-parts":[[2003,6,5]],"date-time":"2003-06-05T16:29:51Z","timestamp":1054830591000},"page":"2501-2507","source":"Crossref","is-referenced-by-count":41,"title":["Two Homozygous Mutations in the 11\u03b2-Hydroxysteroid Dehydrogenase Type 2 Gene in a Case of Apparent Mineralocorticoid Excess"],"prefix":"10.1210","volume":"88","author":[{"given":"Cristian A.","family":"Carvajal","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Internal Medicine (C.A.C., A.A.G., L.M.M., J.A.M., C.E.F.), 114-D Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis A.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine (C.A.C., A.A.G., L.M.M., J.A.M., C.E.F.), 114-D Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian G.","family":"Romero","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (D.G.R., C.E.G.-S.), University of Mississippi Medical Center and the G. 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Montgomery Veterans Affairs Medical Center, Jackson, Mississippi 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Gonza\u0301lez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Center for Genomics and Bioinformatics (A.G., T.O.P.-A.), Pontificia Universidad Cato\u0301lica de Chile, 114-D Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena M.","family":"Mosso","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine (C.A.C., A.A.G., L.M.M., J.A.M., C.E.F.), 114-D Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T.","family":"Lagos","sequence":"additional","affiliation":[{"name":"Department of Nephrology (E.T.L., M.d.P.H., M.P.R.), Hospital San Juan de Dios, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria del P.","family":"Hevia","sequence":"additional","affiliation":[{"name":"Department of Nephrology (E.T.L., M.d.P.H., M.P.R.), Hospital San Juan de Dios, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"Rosati","sequence":"additional","affiliation":[{"name":"Department of Nephrology (E.T.L., M.d.P.H., M.P.R.), Hospital San Juan de Dios, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toma\u0301s O.","family":"Perez-Acle","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Center for Genomics and Bioinformatics (A.G., T.O.P.-A.), Pontificia Universidad Cato\u0301lica de Chile, 114-D Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso E.","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (D.G.R., C.E.G.-S.), University of Mississippi Medical Center and the G. 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Montgomery Veterans Affairs Medical Center, Jackson, Mississippi 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqui\u0301n A.","family":"Montero","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine (C.A.C., A.A.G., L.M.M., J.A.M., C.E.F.), 114-D Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Fardella","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine (C.A.C., A.A.G., L.M.M., J.A.M., C.E.F.), 114-D Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071617560747800_R1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev.nu.16.070196.002303","article-title":"Molecular biology of mineralocorticoid metabolism.","volume":"16","author":"Fardella","year":"1996","journal-title":"Annu Rev 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