Leber congenital amaurosis (LCA) is a term applied to a group of the most severe retinal dystrophies characterized by poor vision (within the first year of life), nystagmus, and a non-recordable electroretinogram. LCA is causing infantile or early childhood blindness.
Variants in CEP290 are the most common cause of LCA10 disease for which there is currently no cure. LCA type 10 is the p.Cys998X pathogenic variant, also known as c.2991+1655A>G mutation in the CEP290 gene. This variant in intron 26 results in aberrant splicing and inclusion of a cryptic exon containing an immediate premature stop codon. As a result, the CEP290 protein is smaller and the cilium shorter than the healthy one. CEP290 plays an important role in cell structures called centrosomes and cilia- microscopic, finger-like projections that stick out from the surface of cells. Cilia are involved in many different chemical signalling pathways and are crucial for the function & survival of photoreceptors. When these light-sensitive ‘photoreceptor’ cells in the layer of tissue at the back of the eye (the retina) degenerate and die, they cause sight loss and eventual blindness.
Currently, LCA is an incurable blinding condition.
- Treatment is mainly supportive and includes correction of refractive error and use of low-vision aids.
- optimal access to educational and work-related opportunities
- Therapies are presently being investigated, including treatments with the use of first-in-class oligonucleotides (ClinicalTrials.gov identifier: NCT03140969) (Clinical Trials Register 2017-000813-22, Belgium – FPS Health-DGM), small molecules, stem cell technologies, gene therapy and gene editing approach.