Clinical heterogeneity in retinitis pigmentosa caused by variants in RP1 and RLBP1 in five extended consanguineous pedigrees

PURPOSE: The aim of this study is to identify disease-causing variants in five consanguineous Jordanian families with a history of autosomal recessive retinitis pigmentosa (RP), and to investigate the clinical variability across the affected individuals. METHODS: Exome sequencing (ES) and ophthalmic examinations were performed to classify the underlying RP-causative variants and their pathogenic consequences. The candidate variants in the affected and unaffected family members underwent segregation analyses with Sanger sequencing. RESULTS: We described four variants in the RP1 and RLBP1 genes as disease-causing across the five families, including novel (c.398delC; p.Pro133GlnfsTer126) and recurrent (c.79delA; p.Thr27ProfsTer26) variants in RLBP1 and two previously reported variants in RP1 ((c.1126C>T; p.Arg376Ter) and (c.607G>A; p.Gly203Arg)). The consequent clinical manifestations were thoroughly investigated using a battery of ophthalmic tests, including electroretinography (ERG), optical coherence tomography (OCT), visual acuity (VA), and fundus examination. The phenotypes indicated clinical heterogeneity, typical RP for variants in RP1, and retinitis punctata albescens (RPA) for variants in RLBP1. CONCLUSIONS: This study extends the pathogenic variant spectrum for the RP1 and RLBP1 genes. The study also revealed the consequent clinical progression, severity, and presentation of RP. Furthermore, we confirm that ES is an efficient molecular diagnostic approach for RP.