Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions.
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.
['Kumaran|Neruban|N|', 'Moore|Anthony T|AT|', 'Weleber|Richard G|RG|', 'Michaelides|Michel|M|']
D000818:Animals D004358:Drug Therapy D015785:Eye Diseases, Hereditary D005136:Eye Proteins D015316:Genetic Therapy D005838:Genotype D006801:Humans D057130:Leber Congenital Amaurosis D008967:Molecular Biology D009154:Mutation D058499:Retinal Dystrophies
leber congenital amaurosis lca eosrd gene therapy review (MeSH terms): retinal diseases early onset severe retinal dystrophy retinal cone photoreceptor cells rtinal rod photoreceptor cells secord severe early childhood onset retinal dystrophy