Retinitis Pigmentosa GTPase Regulator-Associated X-Linked Retinitis Pigmentosa: Molecular Genetics and Clinical Characteristics.
Hwang Sungsoon, Jeon Sohee, Yoon Je Moon, Woo Se Joon, Joo Kwangsic, Choi Yong Je, Yoon Chang Ki, Kim Minjeong, Lee Hyuk Jun, Byeon Suk Ho
AI Summary
This study detailed RPGR-related X-linked RP in Koreans, finding age-specific progression and that truncating variants lead to worse vision, informing gene therapy targeting.
Abstract
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 radius, ellipsoid zone (EZ) bandwidth, 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 open reading frame 15 regions. 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 visual field 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 < .001). Truncating variants were associated with worse VA and a higher risk of complete EZ band loss compared to nontruncating variants (P < .001 and P = .031, respectively).
Conclusions
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.
MeSH Terms
Shields Classification
Key Concepts5
In a retrospective multicenter case series of 133 Korean patients (104 males and 29 females from 107 families) with genetically confirmed RPGR-associated X-linked retinitis pigmentosa, the majority of patients (86.5%) had truncating mutations, and 72.9% of variants were located in the open reading frame 15 regions.
In a retrospective multicenter case series of 133 Korean male patients with genetically confirmed RPGR-associated X-linked retinitis pigmentosa, night blindness onset occurred before the age of 20 in most patients (85%), and worse visual acuity was associated with older age, with the estimated mean best-corrected VA reaching 20/200 by the age of 40.
In a retrospective multicenter case series of 133 Korean male patients with genetically confirmed RPGR-associated X-linked retinitis pigmentosa, more than half of the male patients in their 30s had the widest visual field diameter of less than 20°, and more than three-quarters of patients over 40 were classified in this category.
In a retrospective multicenter case series of 133 Korean patients with genetically confirmed RPGR-associated X-linked retinitis pigmentosa, female carriers generally exhibited a milder phenotype and showed significantly greater interocular asymmetry compared to males (all P < .001).
In a retrospective multicenter case series of 133 Korean patients with genetically confirmed RPGR-associated X-linked retinitis pigmentosa, truncating variants were associated with worse visual acuity and a higher risk of complete ellipsoid zone band loss compared to nontruncating variants (P < .001 and P = .031, respectively).
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