Current genetic screening methods for inherited eye diseases are concentrated on the coding exons of known disease genes (gene panels, clinical exome). These tests have a variable and often limited diagnostic rate depending on the clinical presentation, size of the gene panel and our understanding of the inheritance of the disorder (with examples described in this issue). There are numerous possible explanations for the missing heritability of these cases including undetected variants within the relevant gene (intronic, up/down-stream and structural variants), variants harbored in genes outside the targeted panel, intergenic variants, variants undetectable by the applied technology, complex/non-Mendelian inheritance, and nongenetic phenocopies. In this article we further explore and review methods to investigate these sources of missing heritability.
Keywords: enhancer; regulatory; variant.
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