Abstract
Basel exon skipping - a novel model of disease pathogenesis to explain CEP290-associated retinal degeneration and related ciliopathies
Journal of vision (Charlottesville, Va.), Vol.14(15), pp.85-85
12/29/2014
DOI: 10.1167/14.15.85
Abstract
Centrosomal Protein of 290 kDa (CEP290)-associated mutations are implicated in roughly 25% of cases of Leber congenital amaurosis (LCA), an inherited, retinal degenerative disease that leads to vision loss at an early age. In addition to LCA, the pleiotropic nature of CEP290 mutations manifest in a spectrum of more severe disease states such as Joubert syndrome, Senior-Løken Syndrome and Meckel syndrome. Despite knowing the location of many disease-causing mutations that have been shown to lead to CEP290-associated ciliopathies, explanations for the occurrence of CEP290-related pleiotropy, or that of many other genes, remain unknown. Here, we report that all human CEP290 samples tested demonstrated low levels of exon skipping. Using this observation, a model by which patient genotype can be used to accurately predict CEP290 protein levels as well as disease phenotype was generated. In addition, this model was validated using another unrelated disease gene, CC2D2A. Taken together, we report a novel model of disease pathogenesis that appears to explain, for the first time, the pleiotropic nature of CEP290 and CC2D2A-associated disease and which could potentially be extended to describe observed pleiotropy in other inherited conditions resulting from mutations in a single gene.
Details
- Title: Subtitle
- Basel exon skipping - a novel model of disease pathogenesis to explain CEP290-associated retinal degeneration and related ciliopathies
- Creators
- Adam WojnoTheodore DrivasBudd TuckerEdwin StoneJean Bennett
- Resource Type
- Abstract
- Publication Details
- Journal of vision (Charlottesville, Va.), Vol.14(15), pp.85-85
- DOI
- 10.1167/14.15.85
- ISSN
- 1534-7362
- eISSN
- 1534-7362
- Language
- English
- Date published
- 12/29/2014
- Academic Unit
- Ophthalmology and Visual Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984072081902771
Metrics
14 Record Views