RPGR-associated X-linked Retinitis Pigmentosa: Molecular Genetics and Clinical Characteristics.

Purpose: To describe in detail the genetic profile, clinical features, and genotype-phenotype correlation of retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (RP) in Koreans.

Design: A retrospective multicenter case series.

Methods: This study recruited genetically confirmed RPGR-associated X-linked RP patients from nine tertiary hospitals and clinics across Korea. Genetic profiles, age at night blindness onset, visual acuity (VA), visual field (VF) radius, ellipsoid zone (EZ) band width, bone spicule pigmentation, fundus autofluorescence (AF) pattern, and genotype-phenotype correlation were analyzed.

Results: A total of 133 patients (104 males and 29 females from 107 families) with pathogenic or likely pathogenic RPGR variants were included. The majority of patients (86.5%) had truncating mutations, and 72.9% of variants located in the ORF15 region. In male patients, night blindness onset occurred before the age of 20 in most patients (85%). Worse VA was associated with older age, with the estimated mean best-corrected VA reaching 20/200 by the age of 40 in male. More than half of the male patients in their 30s had the widest VF diameter of less than 20°, and more than three-quarters of patients over 40 were classified in this category. Complete loss of the EZ band was rare before the age of 30; however, more than half of the patients in their 30s exhibited complete EZ band loss. Bone spicule pigmentation was uncommon before the age of 20 (10% of those under 10 and 35% in their teens), whereas peripheral hypoAF pattern was commonly observed after the age of 10 (22% of those under 10 and 81% in their teens). Female carriers generally exhibited a milder phenotype and showed significantly greater interocular asymmetry compared to males (all p<0.001). Truncating variants were associated with worse VA and a higher risk of complete EZ band loss compared to non-truncating variants (p<0.001 and p=0.031, respectively).

Conclusion: This study provides a detailed genetic and age-specific clinical profile of RPGR-related X-linked RP, demonstrating significant differences in phenotypic severity based on the genotype. Our findings provide insights for estimating potential RPGR gene therapy candidate populations, supporting future clinical applications.