Introduction: Retinitis pigmentosa (RP) is a rare degenerative retinal disease caused by mutations in approximately seventy genes. Currently, despite the availability of large-scale DNA sequencing technologies, ~30-40% of patients still cannot be diagnosed at the molecular level. In this study, we investigate a novel intronic deletion of PDE6B, encoding the beta subunit of phosphodiesterase 6, in association with recessive RP. Methods: Three unrelated consanguineous families were recruited from the North-Western part of Pakistan. Whole exome sequencing was performed for the probands of each family and the data were analyzed according to an in-house computer pipeline. Relevant DNA variants in all available members of these families were assessed through Sanger sequencing. A minigene-based splicing assay was also performed. Results: The clinical phenotype for all patients was compatible with rod cone degeneration, with onset during childhood. Whole exome sequencing revealed a homozygous 18 bp intronic deletion (NM_000283.3: c.1921-20_1921-3del) in PDE6B, which co-segregated with disease in 10 affected individuals. In-vitro splicing tests showed that this deletion causes aberrant RNA splicing of the gene, leading to the in-frame deletion of 6 codons and likely to disease. Discussion/Conclusion: Our findings further expand the mutational spectrum of the PDE6B gene.

The Author(s). Published by S. Karger AG, Basel