{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T16:23:07Z","timestamp":1767889387093,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T00:00:00Z","timestamp":1477267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Human Genetics Conference (ESHG)"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Despite being the third most common <jats:italic><jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4<\/jats:italic> variant observed in patients with Stargardt disease, the functional effect of the intronic <jats:italic><jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4<\/jats:italic> variant c.5461\u201010T&gt;C is unknown. The purpose of this study was to investigate the molecular effect of this variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fibroblast samples from patients carrying the <jats:italic><jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4<\/jats:italic> variant c.5461\u201010T&gt;C were analysed by isolating total <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>, followed by real\u2010time polymerase chain reaction (RT\u2010PCR) using specific primers spanning the variant. For detection of <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4 protein, fibroblast samples were lysed and analysed by <jats:styled-content style=\"fixed-case\">SDS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PAGE<\/jats:styled-content> followed by immunoblotting using a monoclonal <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4 antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic><jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4<\/jats:italic> variant c.5461\u201010T&gt;C causes a splicing defect resulting in the reduction of full\u2010length <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> in fibroblasts from patients and the presence of alternatively spliced <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>s where exon 39\u201340 is skipped. A reduced level of full\u2010length <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4 protein is observed compared to controls not carrying the variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study describes the functional effect and the molecular mechanism of the pathogenic <jats:italic><jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4<\/jats:italic> variant c.5461\u201010T&gt;C. The variant is functionally important as it leads to splicing defects and a reduced level of <jats:styled-content style=\"fixed-case\">ABCA<\/jats:styled-content>4 protein.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.13273","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T09:23:58Z","timestamp":1477301038000},"page":"240-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The intronic <i><scp>ABCA<\/scp>4<\/i> c.5461\u201010T&gt;C variant, frequently seen in patients with Stargardt disease, causes splice defects and reduced <scp>ABCA<\/scp>4 protein level"],"prefix":"10.1111","volume":"95","author":[{"given":"Ingvild","family":"Aukrust","sequence":"first","affiliation":[{"name":"Center for Medical Genetics and Molecular Medicine Haukeland University Hospital Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ragnhild 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