Clinical & experimental ophthalmology · 2026
Clinical and Genetic Landscape of RPGR -Associated Retinal Dystrophies in Portugal: Insights From the Nationwide IRD-PT Registry.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Cruz Nuno, Soares Célia Azevedo, Marta Ana, Costa José, Marques-Couto Pedro, Estrela-Silva Sérgio, Madeira Carolina, Anjos Rita, Cabral Diogo, Vaz-Pereira Sara, Alves Henrique, Carvalho Ana Luísa, Marques João Pedro
Аннотация
BACKGROUND: Retinitis pigmentosa GTPase regulator (RPGR)-associated retinal dystrophies are among the most severe inherited retinal diseases (IRDs), yet population-level data from Southern Europe remain scarce.
METHODS: This nationwide, multicentre study characterises the clinical and genetic spectrum of RPGR-associated disease in Portugal, integrating multimodal imaging, standardised phenotyping and curated molecular analysis.
RESULTS: A total of 103 individuals from 40 families (58 males; 45 heterozygous females) were identified using the IRD-PT registry. Males predominantly manifested X-linked retinitis pigmentosa (82.8%) with childhood/adolescence onset (mean 13.1 ± 8.8 years), whereas cone/cone-rod dystrophy (17.2%) presented later in life. Visual acuity in males (mean 0.65 ± 0.54 logMAR) matched international cohorts, showing an age-dependent decline. Female heterozygotes demonstrated striking variability: although central vision was generally preserved (mean 0.39 ± 0.55 logMAR), fundus autofluorescence (FAF) revealed a wide spectrum from normal to male-pattern disease. FAF severity correlated strongly with visual acuity, with male-pattern heterozygotes showing significantly reduced visual acuity. Interocular asymmetry was present in 20.5% of females. Twenty-nine distinct RPGR variants were identified, including 11 novel; truncating variants predominated, particularly within ORF15, accounting for 63% of genetically confirmed cases. Genotype-phenotype relationships aligned with established patterns, with distal RPGR variants associated with cone-dominant disease and proximal variants with rod-cone dystrophy.
CONCLUSIONS: This study provides the first nationwide overview of RPGR-associated disease in Portugal, expanding the mutational landscape and reinforcing the clinical utility of FAF phenotyping in female heterozygotes. These findings support harmonised phenotyping and full-length RPGR sequencing to improve diagnosis, counselling, and readiness for emerging gene-based therapies.
METHODS: This nationwide, multicentre study characterises the clinical and genetic spectrum of RPGR-associated disease in Portugal, integrating multimodal imaging, standardised phenotyping and curated molecular analysis.
RESULTS: A total of 103 individuals from 40 families (58 males; 45 heterozygous females) were identified using the IRD-PT registry. Males predominantly manifested X-linked retinitis pigmentosa (82.8%) with childhood/adolescence onset (mean 13.1 ± 8.8 years), whereas cone/cone-rod dystrophy (17.2%) presented later in life. Visual acuity in males (mean 0.65 ± 0.54 logMAR) matched international cohorts, showing an age-dependent decline. Female heterozygotes demonstrated striking variability: although central vision was generally preserved (mean 0.39 ± 0.55 logMAR), fundus autofluorescence (FAF) revealed a wide spectrum from normal to male-pattern disease. FAF severity correlated strongly with visual acuity, with male-pattern heterozygotes showing significantly reduced visual acuity. Interocular asymmetry was present in 20.5% of females. Twenty-nine distinct RPGR variants were identified, including 11 novel; truncating variants predominated, particularly within ORF15, accounting for 63% of genetically confirmed cases. Genotype-phenotype relationships aligned with established patterns, with distal RPGR variants associated with cone-dominant disease and proximal variants with rod-cone dystrophy.
CONCLUSIONS: This study provides the first nationwide overview of RPGR-associated disease in Portugal, expanding the mutational landscape and reinforcing the clinical utility of FAF phenotyping in female heterozygotes. These findings support harmonised phenotyping and full-length RPGR sequencing to improve diagnosis, counselling, and readiness for emerging gene-based therapies.