Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions
| Autor: | Kumaran, Neruban, Moore, Anthony, Weleber, Richard, Michaelides, Michel |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Eye Diseases
genetic structures Genotype lca Leber Congenital Amaurosis review Review Drug Therapy Retinal Dystrophies Animals Humans Eye Proteins Molecular Biology eosrd rtinal rod photoreceptor cells Eye Diseases Hereditary Genetic Therapy secord retinal cone photoreceptor cells (MeSH terms): retinal diseases gene therapy eye diseases Miscellaneous retinal diseases [(MeSH terms)] Hereditary Mutation sense organs severe early childhood onset retinal dystrophy early onset severe retinal dystrophy |
| Zdroj: | The British Journal of Ophthalmology British Journal of Ophthalmology, vol 101, iss 9 |
| ISSN: | 1468-2079 |
| Popis: | Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. |
| Databáze: | OpenAIRE |
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