{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T03:07:54Z","timestamp":1788750474230,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bartter syndrome type 1, an autosomal recessive genetic disorder, is caused by pathogenic loss\u2010of\u2010function variants in the\n                      <jats:italic>SLC12A1<\/jats:italic>\n                      gene. It is characterized by metabolic alkalosis and prenatal\u2010onset polyuria leading to polyhydramnios.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified pathogenic gene in a 12\u2010day\u2010old newborn boy with Bartter syndrome type 1 using whole\u2010exome sequencing. Sanger sequencing validated the identified variants. A minigene assay was performed to investigate the effect of a novel splice site variant on pre\u2010mRNA splicing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found a compound heterozygous variants in the\n                      <jats:italic>SLC12A1<\/jats:italic>\n                      gene, consisting of a known pathogenic missense mutation (NM_000338: c.769 G&gt;A; p.Gly257Ser) and a novel splice site variant (c.1684+1 G&gt;A). In silico predictions and an in vitro minigene splicing assay demonstrated that the splicing variant c.1684+1 G&gt;A abolished a consensus splice donor site of\n                      <jats:italic>SLC12A1<\/jats:italic>\n                      intron 13, resulting in complete exon 13 skipping, translational frameshift, and premature termination codon, ultimately leading to loss of\n                      <jats:italic>SLC12A1<\/jats:italic>\n                      function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Using a cell\u2010based in vitro assay, we revealed the aberrant effect of the pathogenic splicing variant\n                      <jats:italic>SLC12A1<\/jats:italic>\n                      c.1684+1 G&gt;A on pre\u2010mRNA splicing. Our findings expand the gene mutation spectrum of Bartter syndrome type 1, providing a basis for genetic diagnosis and the development of genetic medicines.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/nep14390-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.14390","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T08:49:09Z","timestamp":1726044549000},"page":"801-805","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>SLC12A1<\/i>\n                    variant c.1684+1 G&gt;A causes Bartter syndrome type 1 by promoting exon 13 skipping"],"prefix":"10.1111","volume":"29","author":[{"given":"Wenke","family":"Yang","sequence":"first","affiliation":[{"name":"Henan Provincial People's Hospital People's Hospital of Henan University, People's Hospital of Zhengzhou University  Zhengzhou China"},{"name":"National Health Commission Key Laboratory of Birth Defects Prevention Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Li","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital People's Hospital of Henan University, People's Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenglong","family":"Guo","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital People's Hospital of Henan University, People's Hospital of Zhengzhou University  Zhengzhou China"},{"name":"National Health Commission Key Laboratory of Birth Defects Prevention Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Ren","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital People's Hospital of Henan University, People's Hospital of Zhengzhou University  Zhengzhou China"},{"name":"National Health Commission Key Laboratory of Birth Defects Prevention Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics  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