{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:47:51Z","timestamp":1773420471957,"version":"3.50.1"},"reference-count":31,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81770662"],"award-info":[{"award-number":["81770662"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81530023"],"award-info":[{"award-number":["81530023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["and 81470928"],"award-info":[{"award-number":["and 81470928"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province (Jiangxi Province natural Science Fund)","doi-asserted-by":"publisher","award":["BL2014007 and BK20141079"],"award-info":[{"award-number":["BL2014007 and BK20141079"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:p>Inactivated variants in CLCNKB gene encoding the basolateral chloride channel ClC-Kb cause classic Bartter syndrome characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here, we identified two cBS siblings presenting hypokalemia in a Chinese family due to novel compound heterozygous CLCNKB mutations (c.848_850delTCT\/c.1755A&gt;G). Compound heterozygosity was confirmed by amplifying and sequencing the patient\u02bcs genomic DNA. The synonymous mutation c.1755A&gt;G (Thr585Thr) was located at +2 bp from the 5\u2032 splice donor site in exon 15. Further transcript analysis demonstrated that this single nucleotide mutation causes exclusion of exon 15 in the cDNA from the proband and his mother. Furthermore, we investigated the expression and protein trafficking change of c.848_850delTCT (\u0394TCT) and exon 15 deletion (\u0394E15) mutation in vitro. The \u0394E15 mutation markedly decreased the expression of ClC-Kb and resulted in a low-molecular-weight band (~55 kDa) trapping in the endoplasmic reticulum, while the \u0394TCT mutant only decreased the total and plasma membrane ClC-Kb protein expression but did not affect the subcellular localization. Finally, we studied the physiological functions of mutations by using whole cell patch-clamp and found that the \u0394E15 or \u0394TCT mutation decreased the current of the ClC-Kb\/barttin channel. These results suggested that the compound defective mutations of the CLCNKB gene are the molecular mechanism of the two cBS siblings.<\/jats:p>","DOI":"10.1152\/ajprenal.00077.2017","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T15:24:18Z","timestamp":1518621858000},"page":"F844-F851","source":"Crossref","is-referenced-by-count":5,"title":["Novel compound heterozygous<i>CLCNKB<\/i>gene mutations (c.1755A&gt;G\/c.848_850delTCT) cause classic Bartter syndrome"],"prefix":"10.1152","volume":"315","author":[{"given":"Chunli","family":"Wang","sequence":"first","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics, Children\u2019s Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital of Nanjing Medical University, Nanjing, 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