A novel heterozygous mutation in PRPH2/RDS gene causing a spectrum of phenotypic manifestations in a family with autosomal dominant retinitis pigmentosa (adRP)

Abstract

Purpose : Retinitis pigmentosa (RP) is a hereditary group of clinically and genetically heterogeneous retinal dystrophies that eventually lead to blindness. The genetics of RP are still incomplete despite intense studies. Currently, about 50 genes explain ~50% of cases. We studied a Canadian family of Syrian origin with adRP and aimed to identify the causal gene.

Methods : Next generation sequencing, family linkage analysis using Affymetrix Human Map 250K Nsp Array and exome capture (AROS, Denmark) were sequentially performed on selected patients. The disease locus was mapped to chromosome 6p, close to the PRPH2/RDS gene. PCR based Sanquer sequencing of the PRPH2/RDS gene was performed in order to identify the novel mutation. Phenotypes were characterized by visual acuity, funduscopy, Goldmann visual fields, OCT (Heidelberg Engineering Inc, Germany), fundus autofluorescence and ERG.

Results : A novel heterozygous mutation in PRPH2/RDS (del352_356TGCTGinsCT) in all affected individuals was identified. The mutation was associated with a wide spectrum of phenotypic manifestations. In particular, the initial proband (MOGL 322) showed severe progressive disease with non-recordable ERGs as well as typical tunnel vision constriction while other patients showed normal fundi and FAF and abnormal ERGs.

Conclusions : We have successfully identified a novel mutation in PRPH2/RDS leading to adRP. The full extent of the mutation spectrum and severity is currently being investigated. Our findings are crucial in expanding the current understanding of inherited retinal blinding diseases in order to provide new avenues for therapeutic interventions and help in patients’ counselling.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.