Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review

Phototransduction, the process by which captured photons elicit electrical changes in retinal rod and cone cells, represents the first neuronal step in vision and involves interactions between several highly specialised proteins. Pathogenic variants in genes encoding many of these proteins can give rise to significant vision impairment, accounting for a substantial portion of inherited retinal disease. Such genes include RHO, OPN1LW, OPN1MW, GNAT1, GNAT2, GNB3, PDE6A, PDE6B, PDE6G, PDE6C, PDE6H, CNGA1, CNGB1, CNGA3, CNGB3, GRK1, SAG, ARR3, RGS9, RGS9BP, GUCY2D, GUCA1A and SLC24A1. Many of these conditions have distinct mechanisms and clinical features. They follow several modes of inheritance (including in one case digenic, or tri-allelic, inheritance). Some conditions also entail myopia. Rod and cone phototransduction will be outlined, followed by the discussion of diseases associated with these genes. Some phenotypic features will be highlighted as well as their prevalence in a large genotyped inherited retinal disease cohort.