1. Fig. 1. A model to explain the pleiotropy of CEP290 disease.
A model to explain the pleiotropy of CEP290 disease. (A) A schematic of nonsense-induced alternative splicing. (I and III) A gene transcript containing a nonsense mutation (red line) undergoes canonical splicing. In both cases, the inclusion of the exon harboring the nonsense mutation targets the transcript for nonsense-mediated decay. (II) Alternative splicing yields a transcript lacking exon 2 and the premature stop codon. The message persists and results in a truncated but otherwise intact open reading frame. (IV) Alternative splicing yields a transcript lacking exon 3 and the premature stop codon but containing a frameshift from the splicing together of incompatible exon ends, resulting in nonsense-mediated decay. (B) A model for predicting CEP290 protein production in individual patients for whom both CEP290 disease alleles are known (fig. S1). Listed below the model are the CEP290 disease phenotypes predicted to be associated with each protein amount.
Theodore G. Drivas et al., Sci Transl Med 2015;7:291ra97
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