Clinical heterogeneity in retinitis pigmentosa caused by variants in and 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 and genes as disease-causing across the five families, including novel (c.398delC; p.Pro133GlnfsTer126) and recurrent (c.79delA; p.Thr27ProfsTer26) variants in and two previously reported variants in ((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 , and retinitis punctata albescens (RPA) for variants in .

Conclusions: This study extends the pathogenic variant spectrum for the and 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.