{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:55:39Z","timestamp":1753890939982,"version":"3.41.2"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017554","name":"Zhejiang Provincial Government Scholarship","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The Gitelman syndrome (GS) is an autosomal recessive disorder of renal tubular salt handling. Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation, and is caused by variants in the <jats:italic>SLC12A3<\/jats:italic> gene. Gitelman syndrome has a heterogeneous phenotype, which may or may not include a range of clinical signs, posing certain difficulties for clinical diagnosis.<\/jats:p><jats:p><jats:bold>Case presentation:<\/jats:bold> A 49-year-old man was admitted to our hospital due to muscular weakness. The patient\u2019s history revealed previous recurrent muscular weakness events associated with hypokalemia, featured by a minimum serum potassium value of 2.3\u00a0mmol\/L. The reported male patient had persistent hypokalemia, hypocalciuria and normal blood pressure, without presenting obvious metabolic alkalosis, growth retardation, hypomagnesemia, hypochloremia or RAAS activation. We performed whole-exome sequencing and identified a novel compound heterozygous variant in the <jats:italic>SLC12A3<\/jats:italic> gene, c.965-1_976delGCGGACATTTTTGinsACCGAAAATTTT in exon8 and c.1112T&amp;gt;C in exon9 in the proband.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This is a study to report a heterogeneous phenotype Gitelman syndrome with a novel pathogenic compound heterozygous variant in the <jats:italic>SLC12A3<\/jats:italic> gene<jats:italic>.<\/jats:italic> This genetic study expands the variants spectrum, and improve the diagnostic accuracy of Gitelman syndrome. Meanwhile, further functional studies are required to investigate the pathophysiological mechanisms of Gitelman syndrome.<\/jats:p>","DOI":"10.3389\/fgene.2023.1067242","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T04:21:00Z","timestamp":1686543660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel compound heterozygous variants of SLC12A3 gene in a Chinese patient with Gitelman syndrome: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Wenqing","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.kint.2016.09.046","article-title":"Gitelman syndrome: Consensus and guidance from a kidney disease: Improving global outcomes (KDIGO) controversies conference","volume":"91","author":"Blanchard","year":"2017","journal-title":"Kidney Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1093\/ndt\/gfn619","article-title":"Heterozygous variants of the sodium chloride cotransporter in Chinese children: Prevalence and association with blood pressure","volume":"24","author":"Hsu","year":"2009","journal-title":"Nephrol. 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