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The consequences of these delins variants on splicing cannot be predicted with certainty without supporting in vitro data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Candidate <jats:italic>ABCA4<\/jats:italic> variants were revealed by genetic and segregation analysis of a family with pseudodominant Stargardt disease using a commercial panel and Sanger sequencing. RNA extracted from patient\u2010derived fibroblasts was analyzed by RT\u2010PCR to evaluate splicing behavior of the <jats:italic>ABCA4<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Affected members carrying the novel c.6031_6044delinsAGTATTTAACCAATATTT variant in exon 44 presented with contrasting phenotypes; from early\u2010onset cone\u2010rod dystrophy to late\u2010onset macular dystrophy. This variant resulted in a 56\u2010nucleotide deletion in the mutant allele by activation of a cryptic splice acceptor site which disrupts the reading frame and results in a premature termination codon (p.Ile2003LeufsTer41). If translated, the crucial functional domains near the C\u2010terminus would be truncated from the ABCA4 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This work demonstrates the intrafamilial phenotypic variability in a pseudodominant Stargardt disease pedigree and the use of patient\u2010derived fibroblasts to evaluate the effect of a novel <jats:italic>ABCA4<\/jats:italic> delins variant on splicing to complement in silico pathogenicity assessment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1259","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T05:46:30Z","timestamp":1587707190000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Phenotype\u2013genotype correlations in a pseudodominant Stargardt disease pedigree due to a novel <i>ABCA4<\/i> deletion\u2013insertion variant causing a splicing 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