{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:04:02Z","timestamp":1789736642289,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>SLC26A4<\/jats:italic> is the second most common cause of hereditary hearing loss worldwide. This gene predominantly harbors pathogenic variants, including splice, nonsense, and missense. Although missense variants are relatively common, their specific effects on protein function remain unclear. Consequently, there is an urgent need to establish an in\u00a0vitro system to investigate how these variants impact <jats:italic>SLC26A4<\/jats:italic> protein function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic testing was conducted to determine the specific types of underlying genetic variants in patients. Following this, we employed plasmid transfection to evaluate the effects of the variants on both protein expression levels and the protein's subcellular localization. Thereafter, we transformed peripheral blood mononuclear cells (PBMCs) from the proband into induced pluripotent stem cells (iPSCs) through Sendai virus\u2010mediated transduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic testing revealed that the proband carried compound heterozygous variants: <jats:italic>SLC26A4<\/jats:italic> c.919\u20102A\u2009&gt;\u2009G and c.317C\u2009&gt;\u2009A. The c.317C\u2009&gt;\u2009A variant markedly decreased the expression levels of <jats:italic>SLC26A4<\/jats:italic> mRNA and its encoded protein. Additionally, it led to the protein's accumulation in the cytoplasm as aggregates. We successfully reprogrammed peripheral blood mononuclear cells from the proband into induced pluripotent stem cells (iPSCs) and verified that these iPSCs retained their pluripotency, differentiation potential, and genetic integrity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results provide important insights into the mechanisms by which <jats:italic>SLC26A4<\/jats:italic> gene variants lead to hearing loss.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70098","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T11:38:52Z","timestamp":1745321932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>SLC26A4<\/i> C.<scp>317C<\/scp>\u2009&gt;\u2009A Variant: Functional Analysis and Patient\u2010Derived Induced Pluripotent Stem Line Development"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7379-1554","authenticated-orcid":false,"given":"Yijing","family":"Li","sequence":"first","affiliation":[{"name":"National Center for International Research in Cell and Gene Therapy, Sino\u2010British Research Centre for Molecular Oncology, School of Basic Medical Sciences Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Henan Medical College  Zhengzhou China"},{"name":"Laboratory of Hearing Loss Mechanism Henan Provincial Medical Key Laboratory  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang","family":"Hu","sequence":"additional","affiliation":[{"name":"Precision Medicine Center, Academy of Medical Science, Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou University  Zhengzhou 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