{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T04:09:55Z","timestamp":1749787795447,"version":"3.41.0"},"reference-count":7,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"N\/A"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,30]]},"abstract":"<jats:sec>\n            <jats:title>Rationale:<\/jats:title>\n            <jats:p>The NR3C2 gene, encoding the mineralocorticoid receptor (MR), harbors over 380 rare coding variants that significantly influence mineralocorticoid homeostasis and disease susceptibility. These variants include both loss-of-function mutations linked to renal pseudohypoaldosteronism type 1 and gain-of-function mutations associated with inherited mineralocorticoid hypertension. This case report describes the clinical features of a previously undocumented NR3C2 mutation, Pro701Leu, in a 60-year-old man presenting with hypertension and hyperkalemia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Patient concerns:<\/jats:title>\n            <jats:p>A Caucasian male in his early 60 seconds presented with hypertension, hyperkalemia, and a history of chronic obstructive pulmonary disease, treated hepatitis C, bipolar disorder, and long-standing polysubstance use disorder. Despite a family history suggesting Gordon syndrome, genetic testing revealed a unique Pro701Leu mutation in the NR3C2 gene.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Diagnoses:<\/jats:title>\n            <jats:p>The patient was diagnosed with hypertension, hyperkalemia, and a Pro701Leu mutation in the NR3C2 gene. The mutation was identified via next-generation sequencing, revealing a missense mutation with leucine substituted for proline at codon 701 in exon 5.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Interventions:<\/jats:title>\n            <jats:p>Initial management included potassium level monitoring and treatment with sodium zirconium cyclosilicate. Despite these measures, hyperkalemia persisted. Furosemide and chlorthalidone were trialed, with chlorthalidone discontinued due to hyponatremia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Outcomes:<\/jats:title>\n            <jats:p>The patient\u2019s blood pressure was eventually controlled, and potassium levels normalized with continued furosemide treatment. The Pro701Leu mutation represents the first documented case linked to hyperkalemia and hypertension, suggesting an activating mutation in the MR gene.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Lessons:<\/jats:title>\n            <jats:p>This case highlights the importance of genetic testing in diagnosing complex cases of hypertension and hyperkalemia. The discovery of the Pro701Leu mutation in the NR3C2 gene underscores the need for further research into its pathophysiological mechanisms and therapeutic implications. Early recognition and tailored treatment can improve patient outcomes in similar cases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/md.0000000000041978","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T20:00:38Z","timestamp":1749758438000},"page":"e41978","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Hypertension and hyperkalemia associated with Pro701Leu mutation in the NR3C2 gene: A case report"],"prefix":"10.1097","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4920-5224","authenticated-orcid":false,"given":"Lawrence","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Nephrology, Westchester Medical Center, Poughkeepsie, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Westchester Medical Center, Poughkeepsie, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Westchester Medical Center, Poughkeepsie, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Assante","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Westchester Medical Center, Poughkeepsie, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20250612","doi-asserted-by":"crossref","first-page":"T93","DOI":"10.1530\/JOE-17-0089","article-title":"30 Years of the mineralocorticoid receptor: mineralocorticoid receptor mutations.","volume":"234","author":"Zennaro","year":"2017","journal-title":"J Endocrinol"},{"key":"R2-20250612","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3390\/genes10120986","article-title":"The molecular genetics of Gordon syndrome.","volume":"10","author":"Mabillard","year":"2019","journal-title":"Genes"},{"key":"R3-20250612","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1126\/science.289.5476.119","article-title":"Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.","volume":"289","author":"Geller","year":"2000","journal-title":"Science"},{"key":"R4-20250612","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1210\/en.2002-220708","article-title":"The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related.","volume":"144","author":"Rafestin-Oblin","year":"2003","journal-title":"Endocrinology"},{"key":"R5-20250612","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1291\/hypres.28.703","article-title":"A novel missense mutation, F826Y, in the mineralocorticoid receptor gene in Japanese hypertensives: its implications for clinical phenotypes.","volume":"28","author":"Kamide","year":"2005","journal-title":"Hypertens Res"},{"key":"R6-20250612","doi-asserted-by":"crossref","first-page":"F645","DOI":"10.1152\/ajprenal.00053.2013","article-title":"Aldosterone acutely stimulates NCC activity via a SPAK-mediated pathway.","volume":"305","author":"Ko","year":"2013","journal-title":"Am J Physiol Renal Physiol"},{"key":"R7-20250612","first-page":"145","article-title":"\u201cOutpatient hyperkalemia\u201d syndrome in renal and hypertensive patients with suppressed aldosterone production.","volume":"10","author":"Rado","year":"1979","journal-title":"J Med"}],"container-title":["Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/MD.0000000000041978","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T20:00:39Z","timestamp":1749758439000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/MD.0000000000041978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":7,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.1097\/md.0000000000041978","relation":{},"ISSN":["0025-7974","1536-5964"],"issn-type":[{"value":"0025-7974","type":"print"},{"value":"1536-5964","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]}}}