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Whole exome sequencing (WES) provides a hypothesis-free first examination of IRD patients in either a clinical or research setting to identify the genetic cause of disease. We present a study of IRD in ten families from Alberta, Canada, through the lens of novel gene discovery. We identify the genetic etiology of IRDs in three of the families to be variants in known disease-associated genes, previously missed by clinical investigations. In addition, we identify two potentially novel associations: <jats:italic>LRP1<\/jats:italic> in early-onset drusen formation and <jats:italic>UBE2U<\/jats:italic> in a multi-system condition presenting with retinoschisis, cataracts, learning disabilities, and developmental delay. 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