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Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of <jats:italic>ABCA4<\/jats:italic>, sequencing of the entire <jats:italic>ABCA4<\/jats:italic> gene or whole genome sequencing. <jats:italic>ABCA4<\/jats:italic> c.4539\u2009+\u20092028C\u2009&gt;\u2009T, p.[=\u2009,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour <jats:italic>ABCA4<\/jats:italic> c.4539\u2009+\u20092028C\u2009&gt;\u2009T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that <jats:italic>ABCA4<\/jats:italic> c.4539\u2009+\u20092028C\u2009&gt;\u2009T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.<\/jats:p>","DOI":"10.1038\/s41598-023-35889-9","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T09:02:48Z","timestamp":1686301368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients"],"prefix":"10.1038","volume":"13","author":[{"given":"Laura","family":"Whelan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Dockery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk A. 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