Identifying a molecular mechanism underlying the disease phenotype in Retinitis Pigmentosa individuals carrying mutations in the spliceosomal gene, PRPF8

Retinitis Pigmentosa (RP) is a neurological disease that results progressively in worsening blindness. It is associated with the loss or degeneration of the classic cone and rod photoreceptor cells. RP is genetically heterogeneous being associated with a range of known mutations in retinal pigment epithelium and photoreceptor-specific genes. However, there are also disease-causing mutations in a group of ubiquitously expressed genes encoding core spliceosome components. Surprisingly, mutations in these splicing genes only display an RP phenotype. In this study, we have reprogrammed dermal fibroblasts from two patients bearing the same point mutation in Prpf8 and from two of their unaffected control siblings first into induced pluripotent stem cells, that were further differentiated into photoreceptor cells. Strikingly, we found that these photoreceptor cells are more sensitive to the splicing mutation, as many more alternative splicing defects were identified in this cell type. However, these defects were not observed in photoreceptor-specific genes. Our data suggest that a critical splicing program is affected by the Prpf8 mutation during the differentiation into photoreceptor cells.

Gwendal Dujardin, University of Oxford, Sir William Dunn School of Pathology, England

Invited by Luc PAILLARD


>> Friday 21 December 2018 at 11:00 - IGDR conference room, ground floor, building 4/ Villejean Campus


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