Molecular genetics of human retinal dystrophies

Abstract

Retinal dystrophies are a heterogeneous group of diseases in which the retina degenerates, leading to either partial or complete blindness. The severe and clearly hereditary forms, retinitis pigmentosa (RP) and various macular degenerations, affect approximately 1 in 3000 people, but many more suffer from aging macular dystrophy in later life. Patients with RP present with narrowing visual fields and night blindness, while those with diseases of the macula lose central vision first. Even before the advent of molecular genetics it was evident that these were heterogeneous disorders, with wide variation in severity, mode of inheritance and phenotype. However, with the widespread application of linkage analysis and mutation detection techniques, a complex underlying pathology has now been revealed. In total, 66 distinct non-overlapping genes or gene loci have been implicated in the various forms of retinal dystrophy, with more being reported regularly in the literature. Within the category of non-syndromic RP alone there are at least 22 genes (and probably many more) involved, with further allelic heterogeneity arising from different mutations in the same gene. This complexity presents a problem for those involved in counselling patients, and also compounds the search for therapies. Nevertheless, several lines of research raise the hope of generic treatments applicable to all such patients, while the greater understanding of normal visual function that arises from genetic studies may open up new avenues for therapy.