Background Retinitis pigmentosa (RP) is a genetically and phenotypically heterogeneous inherited type of retinal dystrophy in which the RHO gene is frequently implicated. The missense variant NM₀00539. 3: c. 545G>A, p. (Gly182Asp), has been reported in genetic databases as pathogenic, and a recent large cohort identified a single patient carrying this variant with sector RP. However, no detailed intrafamilial phenotypic characterization has been described. This study provides the first such characterization in a Portuguese family. Case presentation Four individuals across three generations underwent multimodal ophthalmologic evaluations, including visual acuity, fundus imaging (OCT, FAF), visual field testing, and electrophysiology. Three patients underwent genetic testing, and all carried the heterozygous RHO p. (Gly182Asp) variant. The clinical manifestations ranged from typical RP in three members to sector RP in one, with preferential inferior and nasal retinal involvement. Structural and functional severity increased with age, and all presented with nyctalopia. The oldest patient exhibited advanced degeneration with minimal central vision. This intrafamily phenotypic variability underscores the differential expression of the same genotype. Conclusions This is the first report linking the RHO p. (Gly182Asp) variant with both typical and sector RP, highlighting intrafamilial heterogeneity. Detailed phenotyping is crucial for genetic counseling and potential inclusion in future gene-based therapies.
Teixeira-Martins et al. (Thu,) studied this question.