{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:45:33Z","timestamp":1777427133833,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide\u2010sensitive sodium\u2010chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Patients and Measurements<\/jats:title><jats:p>The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both patients were middle\u2010aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin\u2010angiotensin\u2010aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves'\u00a0disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C&gt;T (Thr60Met). The novel c.2159G&gt;T (p. Gly720Val) and c.2675T&gt;C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs\u2014Polyphen\u20102, SIFT, Mutation Taster and LRT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified two novel SLC12A3 genetic variant [c.2159G&gt;T (p.Gly720Val) and c.2675T&gt;C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14870","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T14:30:50Z","timestamp":1671805850000},"page":"474-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7307-3372","authenticated-orcid":false,"given":"Qiao","family":"Ying","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Taizhou Municipal Hospital Taizhou Zhejiang People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhinan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurology Taizhou Municipal Hospital Taizhou Zhejiang People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Taizhou Municipal Hospital Taizhou Zhejiang People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Taizhou Municipal Hospital Taizhou Zhejiang People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linxiong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Taizhou Municipal Hospital Taizhou Zhejiang People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaisang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Taizhou Municipal Hospital 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