{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:58:17Z","timestamp":1786132697518,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract.<\/jats:title>\n                    <jats:p>\n                      Gitelman's syndrome (GS) is an autosomal recessive disorder characterized by metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria that has recently been reported to be linked to thiazide-sensitive Na-Cl cotransporter (TSC) gene mutations. In this study, possible mutations in the TSC gene of six Japanese patients clinically diagnosed with GS were investigated. Twenty-six exons encoding TSC were amplified by PCR and then completely sequenced by the direct sequencing method. Patient A showed a missense mutation of Arg 642 to Cys on the paternal allele and a missense mutation of Val 578 to Met and a 2-bp deletion (nucleotide 2543-2544) on the maternal allele. This deletion results in a frameshift that alters codon 837 to encode a stop signal rather than phenylalanine, and it is predicted to lead to loss of the latter half of the intracellular carboxy terminus. In the second family, two affected sisters, patients B and C, had a homozygous missense mutation of Thr 180 to Lys. Both of their parents, who are consanguineously married, have a heterozygous Thr180Lys mutation. Patient D has a homozygous mutation Thr180Lys, which is the same as the second family. Haplotype analysis indicates that patients B and C are not related to patient D. In patients E and F, we could identify only one mutant allele; Ala569Glu and Leu849His, respectively. All of the mutations identified are novel except for the Arg642Cys mutation, which has been found in a Japanese GS patient. Although further\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      study is required to prove that the mutations are responsible for GS, it is possible that Thr180Lys and Arg642Cys mutations might be common mutations in Japanese GS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.v11165","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T20:52:40Z","timestamp":1620247960000},"page":"65-70","source":"Crossref","is-referenced-by-count":62,"title":["Novel Mutations in Thiazide-Sensitive Na-Cl Cotransporter Gene of Patients with Gitelman's Syndrome"],"prefix":"10.1681","volume":"11","author":[{"given":"TOSHIAKI","family":"MONKAWA","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ISAO","family":"KURIHARA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KAZUO","family":"KOBAYASHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MATSUHIKO","family":"HAYASHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TAKAO","family":"SARUTA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-200001000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:22:54Z","timestamp":1786130574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-200001000-00008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2000]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.v11165","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[2000,1]]}}}