{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:26:20Z","timestamp":1791890780252,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T00:00:00Z","timestamp":1739059200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"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":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alport syndrome involves chronic progressive kidney failure and extrarenal organ damage caused by\n                      <jats:italic>COL4A3<\/jats:italic>\n                      ,\n                      <jats:italic>COL4A4<\/jats:italic>\n                      , and\n                      <jats:italic>COL4A5<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We initially discerned a\n                      <jats:italic>COL4A3<\/jats:italic>\n                      splicing mutation via next\u2010generation sequencing. Next, we used bioinformatics, renal biopsy pathology, and an in\u00a0vitro minigene experiment. Complementary analysis of clinical data was carried out, and we explored the expression and function of the variants to verify their pathogenicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A splicing mutation\n                      <jats:italic>(c.687\u2009+\u20091G\u2009&gt;\u2009T)<\/jats:italic>\n                      in\n                      <jats:italic>COL4A3<\/jats:italic>\n                      was found in a Chinese family. Bioinformatics analysis revealed its impact on splicing, causing a translational frameshift, which was confirmed by an in\u00a0vitro minigene assay. The proband's glomerular basement membrane displayed reduced type IV collagen \u03b13, \u03b14, and \u03b15 chains, with some absent, suggesting disruption of collagen IV trimers in the glomerular basement membrane, potentially damaging the glomerular filtration barrier.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We present a novel finding of a previously unreported\n                      <jats:italic>c.687\u2009+\u20091G\u2009&gt;\u2009T<\/jats:italic>\n                      mutation in\n                      <jats:italic>COL4A3<\/jats:italic>\n                      that disrupts transcription and translation, impairing \u03b13\u03b14\u03b15 (IV) chain formation, altering the integrity of the glomerular basement membrane, causing hereditary Alport syndrome. This discovery enriches the genetic map of Alport syndrome, aiding in clinical genetic guidance, and enhancing the efficacy of prenatal testing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70053","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T20:24:50Z","timestamp":1739219090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of a Novel\n                    <i>COL4A3<\/i>\n                    Homozygous\/Heterozygous Splicing Mutation on the Mild Phenotype in a Family With Autosomal Recessive Alport Syndrome and a Literature Review"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6907-5737","authenticated-orcid":false,"given":"Dan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial 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