{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T01:40:27Z","timestamp":1764639627900,"version":"3.46.0"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Gitelman syndrome (GS) is considered one of the most common hereditary renal tubular disorders, characterised by hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. The primary cause of this disorder resides in the\n SLC12A3<\/jats:italic>\n gene, which encodes the NaCl cotransporter in the distal convoluted tubule, and for which more than 500 mutations associated with GS have been described. We present the case of a 51\u2010year\u2010old female referred for evaluation of recurrent hypokalemia and hypomagnesemia, with no clinical symptoms. The blood test also revealed hypocalciuria and metabolic alkalosis. Oral supplementation with potassium and magnesium was prescribed. A next\u2010generation sequencing (NGS) test was performed on her and her child (no other relatives alive), who was also asymptomatic with no obvious electrolytic abnormalities. Two mutations confirmed as pathogenic were found in the\n SLC12A3<\/jats:italic>\n gene (NM_000339.3) of the mother, c.704C>G and c.704C>T, as well as a new heterozygous variant in trans not reported before, c.704C>A p.(Thr235Lys), and identified as a variant of uncertain significance (VUS). This new VUS (c.704C>A p) was also present in the child, increasing evidence of its potential pathogenicity. The new\n SLC12A3<\/jats:italic>\n gene variant could represent a pathogenic mutation associated with GS. The use of NGS\u2010based panel is recommended to cover the large genotypic variability associated with this disease, in an attempt to identify novel\n SLC12A3<\/jats:italic>\n gene variants of potential pathogenicity.\n <\/jats:p>","DOI":"10.1111\/nep.70127","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T12:34:35Z","timestamp":1757766875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Pathogenic Genotype in\n \n SLC12A3<\/i>\n <\/scp>\n Associated to Gitelman Syndrome: A Case Report"],"prefix":"10.1111","volume":"30","author":[{"given":"Patricia","family":"Tom\u00e1s\u2010Sim\u00f3","sequence":"first","affiliation":[{"name":"Nephrology Department Consorcio Hospital General Universitario de Valencia Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-7239","authenticated-orcid":false,"given":"Antonio","family":"Sierra\u2010Rivera","sequence":"additional","affiliation":[{"name":"Genetics Section, Clinical Analysis Service Consorcio Hospital General Universitario de Valencia Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8958-6711","authenticated-orcid":false,"given":"Ana","family":"Checa\u2010Ros","sequence":"additional","affiliation":[{"name":"Cardiorenal and Metabolic Diseases Research Group, Department of Medicine and Surgery, Faculty of Health Sciences Cardenal Herrera\u2010CEU University, CEU Universities Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-5382","authenticated-orcid":false,"given":"Raquel","family":"Rodr\u00edguez\u2010L\u00f3pez","sequence":"additional","affiliation":[{"name":"Genetics Section, Clinical Analysis Service Consorcio Hospital General Universitario de Valencia Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Gal\u00e1n\u2010Serrano","sequence":"additional","affiliation":[{"name":"Nephrology Department Consorcio Hospital General Universitario de Valencia Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"D'Marco","sequence":"additional","affiliation":[{"name":"Cardiorenal and Metabolic Diseases Research Group, Department of Medicine and Surgery, Faculty of Health Sciences Cardenal Herrera\u2010CEU University, CEU Universities Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.09.046"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.544925"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101755.2001.059002710.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101755.2003.00730.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010090907"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20103\u201022"},{"key":"e_1_2_9_8_1","first-page":"221","article-title":"A New Familial Disorder Characterized by Hypokalemia and Hypomagnesemia","volume":"79","author":"Gitelman H. 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