Heterozygous deletions of noncoding parts of the PRPF31 gene cause retinitis pigmentosa via reduced gene expression
Francesco Paolo Rubertoa, Sara Balzanob, Prasanthi Namburic, Adva Kimchic, Rosanna Pescini Gobertb, Alexey Obolenskyc, Eyal Baninc, Tamar Ben‐Yosefd, Dror Sharonc, Carlo Rivoltae
- aExperimental Cardiology Unit, Department of Cardiovascular Medicine, University of Lausanne Medical School, Lausanne, Switzerland
- bDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland
- cDepartment of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, the Hebrew University of Jerusalem, Jerusalem, Israel
- dRappaport Faculty of Medicine Technion‐Israel Institute of Technology Haifa Israel
- eInstitute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland
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Abstract
Purpose: , encoding a pre-mRNA splicing factor, cause autosomal dominant retinitis pigmentosa (adRP) with reduced penetrance. At the molecular level, pathogenicity results from haploinsufficiency, as the largest majority of such mutations trigger nonsense-mediated mRNA decay or involve large deletions of coding exons. We investigated genetically two families with a history of adRP, one of whom showed incomplete penetrance. Methods: transcripts were quantified with real-time PCR on patient-derived lymphoblastoid cell lines. Results: mRNA from lymphoblastoid cell lines from one of these families showed reduced levels of expression in patients versus controls, probably due to the heterozygous ablation of its promoter sequences. Conclusions: -linked adRP.