Identification of the RPGR Gene Pathogenic Variants in a Cohort of Polish Male Patients with Retinitis Pigmentosa Phenotype

The goal of the study was to explore the spectrum of pathogenic variants in the RPGR gene in a group of male Polish patients with a retinitis pigmentosa (RP) phenotype. A total of 45 male index patients, including twins, being members of 44 families, were screened for pathogenic variants in the RPGR gene via the direct sequencing of PCR-amplified genomic DNA and underwent a comprehensive ophthalmological examination in one center located in Poland. A total of two pathogenic and five likely pathogenic variants in eight patients (18%) were detected in the studied cohort. Of these, five variants were novel, and five disease-causing variants (71%) were identified within the ORF15 mutational hotspot of the RPGR gene. The median age of onset of the disease was 10 years (range 6-14 years), the median age during the examination was 30 years (range 20-47 years), and the median visual acuity was 0.4 (range 0.01-0.7). The majority of patients had middle constriction of the visual field and thinning of the central foveal thickness. Dizygotic twins bearing the same hemizygous mutation showed a different retinal phenotype in regard to the severity of the symptoms. This is the first RPGR mutation screening in Poland showing a prevalence of 18% of RPGR pathogenic mutations and likely pathogenic variants in the studied cohort of male patients with an RP phenotype.

Automated summary

The goal of this study was to explore the spectrum of pathogenic variants in the RPGR gene in male Polish patients with retinitis pigmentosa. The study found 2 pathogenic and 5 likely pathogenic variants in 8 patients (18%), with 5 of the variants being novel and 5 being identified in the ORF15 mutational hotspot of the RPGR gene. The majority of patients had visual field constriction and thinning of the central foveal thickness. Dizygotic twins with the same mutation showed different retinal phenotypes, indicating variations in symptom severity.