{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:41:33Z","timestamp":1790480493577,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Gitelman's syndrome (GS) is an autosomal recessive renal tubular disorder caused by mutations in the\n                      <jats:italic toggle=\"yes\">SLC12A3<\/jats:italic>\n                      gene encoding the thiazide-sensitive Na\n                      <jats:sup>+<\/jats:sup>\n                      -Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      cotransporter (NCC). Despite meticulous sequencing of genomic DNA, approximately one-third of GS patients are negative or heterozygotes for the known mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, Participants, &amp; Measurements<\/jats:title>\n                    <jats:p>\n                      Because blood leukocytes express NCC mRNA, we evaluate whether deep intronic mutations contribute to GS patients with uniallelic or undetectable\n                      <jats:italic toggle=\"yes\">SLC12A3<\/jats:italic>\n                      mutations. Twenty-nine patients with GS (men\/women = 16\/13), including eight negative and 21 uniallelic\n                      <jats:italic toggle=\"yes\">SLC12A3<\/jats:italic>\n                      mutations from 19 unrelated families, and normal controls were enrolled in an academic medical center. Analysis of cDNA from blood leukocytes, sequencing of the corresponding introns of genomic DNA for abnormal transcript, and analysis of NCC protein expression from renal biopsy were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified nine Taiwan aboriginal patients carrying c.1670\u2013191C\u2192T mutations in intron 13 and 10 nonaboriginal patients carrying c.2548+253C\u2192T mutations in intron 21 from 14 families (14\/19). These two mutations undetected in 100 healthy subjects created pseudoexons containing new premature termination codons. Haplotype analysis with markers flanking\n                      <jats:italic toggle=\"yes\">SLC12A3<\/jats:italic>\n                      revealed that both mutations did not have founder effects. Apical NCC expression in the DCT of renal tissue was markedly diminished in two patients carrying deep intronic mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Deep intronic mutations in\n                      <jats:italic toggle=\"yes\">SLC12A3<\/jats:italic>\n                      causing defective NCC expression can be identified with the RNA-based approach in patients with GS. c.1670\u2013191C\u2192T and c.2548+253C\u2192T are hot spot mutations that can be screened in GS patients with uniallelic or negative\n                      <jats:italic toggle=\"yes\">SLC12A3<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.06730810","type":"journal-article","created":{"date-parts":[[2010,11,4]],"date-time":"2010-11-04T22:57:26Z","timestamp":1288911446000},"page":"630-639","source":"Crossref","is-referenced-by-count":63,"title":["Recurrent Deep Intronic Mutations in the SLC12A3 Gene Responsible for Gitelman's Syndrome"],"prefix":"10.2215","volume":"6","author":[{"given":"Yi-Fen","family":"Lo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandai","family":"Nozu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumoto","family":"Iijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Chung","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Sen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Kang","family":"Sytwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wei","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hua","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Hua","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-24-20230811","first-page":"211","article-title":"A 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