{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:54:47Z","timestamp":1790754887793,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170717"],"award-info":[{"award-number":["82170717"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>X\u2010linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of <jats:italic>COL4A5<\/jats:italic> on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre\u2010mRNA by altering various splicing regulatory signals. The male patients with XLAS have a strong genotype\u2013phenotype correlation. Confirming the effect of variants on splicing can help to predict kidney prognosis. This study aimed to investigate whether single nucleotide substitutions, located within three bases at the 5\u2032 end of the exons or internal position of the exons in <jats:italic>COL4A5<\/jats:italic> gene, cause aberrant splicing process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed 401 SNVs previously presumed missense and nonsense variants in <jats:italic>COL4A5<\/jats:italic> gene by bioinformatics programs and identified candidate variants that may affect the splicing of pre\u2010mRNA via minigene assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study indicated three of eight candidate variants induced complete or partial exon skipping. Variants c.2678G&gt;C and c.2918G&gt;A probably disturb classic splice sites leading to corresponding exon skipping. Variant c.3700C&gt;T may disrupt splicing enhancer motifs accompanying with generation of splicing silencer sequences resulting in the skipping of exon 41.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed that two missense variants positioned the first nucleotides of the 5\u2032 end of <jats:italic>COL4A5<\/jats:italic> exons and one internal exonic nonsense variant caused aberrant splicing. Importantly, this study emphasized the necessity of assessing the effects of SNVs at the mRNA level.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2395","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T07:16:02Z","timestamp":1708758962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Three exonic variants in the <scp>COL4A5<\/scp> gene alter <scp>RNA<\/scp> splicing in a minigene assay"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3911-3478","authenticated-orcid":false,"given":"Ran","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Materials the Affiliated Qingdao Municipal 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