RESUMO
Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.
Assuntos
Eletrorretinografia , Periferinas , Fenótipo , Distrofias Retinianas , Acuidade Visual , Humanos , Periferinas/genética , Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Adolescente , Distrofias Retinianas/genética , Distrofias Retinianas/fisiopatologia , Distrofias Retinianas/diagnóstico , Idoso , Acuidade Visual/fisiologia , Criança , Adulto Jovem , Pré-Escolar , Tomografia de Coerência Óptica , Mutação , Angiofluoresceinografia , Estudos de Associação Genética , Estudos Retrospectivos , Análise Mutacional de DNA , DNA/genética , LinhagemRESUMO
BACKGROUND: Heterozygous c.440 G > T mutation in the S-antigen visual arrestin (SAG) gene has been described as a cause of autosomal dominant retinitis pigmentosa (adRP) in a series of patients of Hispanic origin. This study presents the early and late clinical features and disease progression rates in an Australian family with SAG adRP. MATERIALS AND METHODS: An observational case series of four family members with adRP. They were examined clinically, with multi-modal retinal imaging and electroretinography (ERG) to ascertain phenotype. Disease progression rate was measured using optical coherence tomography (OCT) and fundus autofluorescence (FAF). A retinal dystrophy panel was used for the proband and cascade testing with targeted Sanger sequencing was conducted in other available family members. RESULTS: The proband presented at 36 years of age with profoundly reduced full-field ERG responses despite a sector RP phenotype. This progressed to a classic RP pattern over several decades leaving a small residual island of central visual field. The horizontal span of the residual outer nuclear layer and the area of hyperautofluorescent ring contracted at a rate of 8-11% and 9-14% per year, respectively. DNA sequencing confirmed the segregation of SAG c.440 G > T mutation with disease. CONCLUSION: SAG adRP presents with a reduced full-field ERG response consistent with a rod-cone dystrophy in mid-life despite a sector RP phenotype. Centripetal progression of the disease into the macula can be tracked by OCT and FAF imaging.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação a DNA/genética , Mutação , Retinose Pigmentar/patologia , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Austrália , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Retinose Pigmentar/etiologia , Retinose Pigmentar/metabolismo , Campos VisuaisRESUMO
Foveal retinoschisis is rarely found in women. An 11-year-old girl, from non-consanguineous parents, presented with bilateral visual loss from isolated foveal retinoschisis as confirmed by a normal fluorescein angiogram and characteristic optical coherence tomogram. Psychophysical and electrophysiological studies demonstrated mild contrast sensitivity loss, dyschromatopsia and normal full field electroretinographic responses. Visual acuity, foveal retinoschisis, electroretinography, electro-oculography and visual evoked responses remained stable after 13 years but a reduction in pattern electroretinography amplitude was noted. No mutation was found in the coding regions of the RS1 gene. Isolated foveal retinoschisis may be a form of macular dystrophy. Longer-term follow up may contribute to our understanding of this rare disease.