Beyond Sector Retinitis Pigmentosa: Expanding the Phenotype and Natural History of the Rhodopsin Gene Codon 106 Mutation (Gly-to-Arg) in Autosomal Dominant Retinitis Pigmentosa

Abstract

Sector and pericentral are two rare, regional forms of retinitis pigmentosa (RP). While usually defined as stable or only very slowly progressing, the available literature to support this claim is limited. Additionally, few studies have analyzed the spectrum of disease within a particular genotype. We identified all cases (9 patients) with an autosomal dominant Rhodopsin variant previously associated with sector RP (RHO c.316G > A, p.Gly106Arg) at our institution. Clinical histories were reviewed, and testing included visual fields, multimodal imaging, and electroretinography. Patients demonstrated a broad phenotypic spectrum that spanned regional phenotypes from sector-like to pericentral RP, as well as generalized disease. We also present evidence of significant intrafamilial variability in regional phenotypes. Finally, we present the longest-reported follow-up for a patient with RHO-associated sector-like RP, showing progression from sectoral to pericentral disease over three decades. In the absence of comorbid macular disease, the long-term prognosis for central visual acuity is good. However, we found that significant progression of RHO p.Gly106Arg disease can occur over protracted periods, with impact on peripheral vision. Longitudinal widefield imaging and periodic ERG reassessment are likely to aid in monitoring disease progression.

Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker

“…When the implicit time is normal or near normal, sector RP has a stationary or more slowly progressive phenotype. However, patients with very delayed cone flicker implicit time, even if the fundus appears to have "sector RP," have the progressive form of RP (48)(49)(50). Berson et al took this observation further by noting that a patient's initial implicit time can numerically help predict the rate of decline of the residual cone response amplitude (28).…”

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin

“…Clinical features and visual prognosis differ between patients with generalized and sector RP. Although sector RP progresses relatively slower than generalized RP, several reports stated that it eventually progresses to the generalized type ( Ballios et al, 2021 ; Nguyen et al, 2021 ). However, the difference in genetic and clinical features between generalized and sector RP is unclear.…”

Aberrant Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem Cells of a Retinitis Pigmentosa Patient with the PRPF6 Mutation

“…To date, mutations in more than 84 genes and loci have been identified, and 23 of them cause autosomal dominant RP (adRP; RetNet : , last accessed 9 June 2022). The effective treatment of RP remains a major challenge in medicine, as gene therapy for RP is limited by the high genetic heterogeneity of the disease, emphasizing the importance of studying the molecular mechanisms that are independent of mutated genes [ 4 ].…”