Phenotypic Features of Oguchi Disease and Retinitis Pigmentosa in Patients with S-Antigen Mutations

Abstract

To present phenotypic features of 22 patients with S-antigen (SAG) mutations. Design: Retrospective cohort study.Participants: Twenty-one Japanese patients from 16 families with a homozygous c.924delA mutation and 1 patient with a homozygous c.636delT mutation in the SAG gene.Methods: Clinical records on symptoms; best-corrected visual acuity; and Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), OCT, and electroretinography results were reviewed.Main Outcome Measures: Best-corrected visual acuity, Goldmann perimetry results, imaging findings, and electroretinography results.Results: Ten patients had Oguchi disease and 12 had retinitis pigmentosa (RP) with mean follow-up periods of 13.8 and 10.2 years, respectively. Retinitis pigmentosa patients were older (mean age, 56.0 years) than those with Oguchi disease (mean age, 22.1 years; P < 0.001) at the initial visit. Night blindness noted in childhood was the most common initial symptom for both Oguchi disease (80.0%) and RP (91.7%) patients. Best-corrected visual acuity in the logarithm of the minimum angle of resolution (logMAR) was well preserved in Oguchi disease patients (mean, 0.02 logMAR in both eyes) but reduced in most RP patients (mean, 1.32 logMAR [right eye] and 1.35 logMAR [left eye]). Similarly, the visual field in the retinal area was preserved in Oguchi disease patients (mean, 677 mm 2 right eye and 667 mm 2 left eye) and reduced in RP patients (mean, 369 mm 2 right eye and 294 mm 2 left eye). Fundus images revealed a characteristic golden sheen with no retinal degeneration in Oguchi disease patients, excluding 2 with macular degeneration detected by FAF, OCT, or both and 1 with mild retinal degeneration confirmed by OCT and fluorescein angiography. Pigmentary retinal degeneration most evident posteriorly was observed in RP patients, accompanied by a characteristic golden sheen in 12 of 14 patients undergoing ultra-widefield fundus imaging. OCT showed disrupted macular structure, and FAF revealed variable hypofluorescence. Electroretinography identified absent rod responses in both diseases, along with relative preservation of cone responses in Oguchi disease patients. Three patients showed progressive loss of the golden sheen based on fundus images, including 1 who demonstrated RP 26 years after the initial diagnosis of Oguchi disease.Conclusions: Retinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP.

Optical Coherence Tomography of Animal Models of Retinitis Pigmentosa: From Animal Studies to Clinical Applications

“…Previous studies have revealed that mutations in the Arrestin 1 gene ( Arr 1 , also abbreviated as SAG , soluble antigen) cause Oguchi disease, a type of autosomal recessive “stationary” night blindness [72] or autosomal recessive RP [73]. Recently, Nishiguchi and associates reported that patients with Arr 1 ( SAG ) gene mutations show phenotypic heterogeneity varying from stationary Oguchi type to progressive RP type [74]. Thus, the Arr1 –/– mice can be considered to be a mouse model of RP [75].…”

Systematic detection of Mendelian and non-Mendelian variants associated with retinitis pigmentosa by genome-wide association study

“…The sequenced reads were aligned to the human reference genome using BWA-mem (ver. Sanger sequencing was carried out for genotyping of family members using the protocol described earlier 45 . In brief, genomic DNA was amplified with PCR using Amplitaq agarose gel with appropriate controls and markers.…”

New variants and in silico analyses in GRK1 associated Oguchi disease

“…Electrophysiologically there is normal cone function, delayed rod dark adaptation and marked rod desensitization to a bright flash. Most reported cases have this distinctive phenotype and no significant variation in disease expression has been reported, with the exception of a few rare cases (Hayashi et al, 2007; Nishiguchi et al, 2019). Distinguishing between Oguchi disease and other forms of CSNB is important as they may have different prognoses—some patients with Oguchi disease report very slowly progressive visual dysfunction, whereas those with classical CSNB do not.…”

“…Electrophysiologically there is normal cone function, delayed rod dark adaptation and marked rod desensitization to a bright flash. Most reported cases have this distinctive phenotype and no significant variation in disease expression has been reported, with the exception of a few rare cases (Hayashi et al, 2007;Nishiguchi et al, 2019). POULTER ET AL.…”