Abstract
Purpose :
Topoisomerase I–binding RS protein (TOPORS), a ubiquitous multidomain protein involved in cell cycle regulation and protein synthesis, has been shown to be susceptible to a variety of mutations and is responsible for about 1% of autosomal dominant retinitis pigmentosa (adRP). We aim to document various genotype/phenotype relations present in Rural Appalachia due to the rare nature of such mutations.
Methods :
Charts of 208 patients with inherited retinal disease were reviewed for mutations in TOPORS. All patients had undergone genetic testing in their families at the WVU Eye Institute from 2015 to 2020. A system-wide research query engine (Slicer Dicer - Epic Systems) was used to identify the study population via patient identifier numbers and ICD codes.
Results :
A total of six patients (ages 10-70) were identified amongst three families. Mutations in TOPORS accounted for about 2.8% of all adRP cases at our institution. All patients were female. The average follow-up was 9 years (0-18).
A mother (70 yr) and daughter (50 yr) had a novel heterozygous missense point mutation in TOPORS c.2431C > T, p.Gln811X (Exon 3) altering the glutamine codon (CAG) into a stop codon (TAG) causing premature truncation of the protein. Cataract, severe loss of visual field, cystoid edema, and a full-thickness macular hole with successful repair were complications seen in the mother. Her daughter also had chronic macular edema and profound visual field loss.
Four patients with frameshift variant c.2556_2557del,p.(Glu852Aspfl*20) had no macular edema and minimal cataract during follow-up. Visual field loss was progressive with age.
Conclusions :
We identified six patients, two of which had novel truncating variants of the TOPORS gene. Patients with this new variant had profound night blindness and visual field loss, recurrent macular edema, and in one individual, epiretinal membrane leading to a macular hole in one eye. Similar missense mutations have been previously described and appear to make up most of the mutational variants which have been shown to lead to early degradation of the TOPORS and subsequently early onset retinal degeneration.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.