Figure 4.

Flow-scheme of genetic tests that should be performed in patients with inherited eye disorders. In our exome approach, some regions of genes associated with inherited eye disorders have consistently low or no coverage. For instance, regions with high homology, GC-rich regions and repetitive regions are difficult to enrich. Moreover, deep-intronic and small copy number variations are not detected via an exome-sequencing approach. To provide the best care, a diagnostic flow-scheme specific for our exome approach was developed, to provide an overview in which types of inherited eye disorders a genetic test should be performed as a pre-screen or after a negative exome result. In patients with Leber congenital amaurosis, Stargardt disease, X-linked retinitis pigmentosa, blue cone monochromacy, Bornholm eye disease and albinism, a genetic pre-screen of one or two specific genes is indicated. In simplex male patients with retinitis pigmentosa or cone–rod dystrophy and in patients with X-linked cone–rod dystrophy, a genetic follow-up test of one or two specific genes is indicated after a negative exome result. In patients in whom a single heterozygous pathogenic variant is detected in a gene associated with autosomal recessive inheritance, it is indicated to test the non-covered regions of that gene.