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Purpose: Mutations in Topoisomerase I–binding RS protein (TOPORS) have been previously documented and have been described to result in pathological autosomal dominant retinitis pigmentosa (adRP). In our study, we describe the various genotypes and clinical/phenotypic manifestations of TOPORS-related mutations of our unique patient population in Rural Appalachia. Methods: The medical records of 416 patients with inherited retinal disease at the West Virginia University Eye Institute who had undergone genetic testing between the years of 2015–2022 were reviewed. Patients found to have pathologic RP and mutations related to TOPORS were then analyzed. Results: In total, 7 patients (ages 12–70) were identified amongst three unique families. All patients were female in our study. The average follow-up period was 7.7 years. A mother (70 yr) and daughter (51 yr) had a novel heterozygous nonsense point mutation in TOPORS c.2431C > T, p.Gln811X (Exon 3) that led to premature termination of the desired protein resulting in early onset vision loss, cataract formation, and visual field restriction. The mother developed a full-thickness macular hole which was successfully repaired. Five other patients were found to have previously described TOPORS mutations. Visual field loss was progressive with age in both cohorts. Conclusions: Seven patients at our institution were identified to have mutations in TOPORS resulting in autosomal dominant retinitis pigmentosa. Two patients were found to have novel truncating mutations in the TOPORS gene resulting in profound night blindness and visual field loss, recurrent macular edema, and in one individual, epiretinal membrane formation leading to a macular hole which was able to be successfully repaired. [ABSTRACT FROM AUTHOR]

Recessive Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) mutations can cause early onset muscle–eye–brain disease but have also more recently been associated with non-syndromic Retinitis Pigmentosa. In this case series, we describe three sisters affected by non-syndromic autosomal recessive POMGNT1 retinopathy with a report of a new variant. The three patients received care at West Virginia University Eye Institute, including full ophthalmic examination with additional fundus imaging, optical coherence tomography (OCT), electroretinogram (ERG), and visual field testing. Diagnostic panel testing of 330 genes was also obtained. The proband was seen for cataract evaluation at age 42, and her fundus examination was suggestive of retinitis pigmentosa. Her oldest sister had been treated for acute anterior uveitis with retinal vasculitis. Another sister was diagnosed with multiple sclerosis (MS) and peripheral retinal degeneration. Posterior subcapsular cataracts were diagnosed between age 42 and 55 in all three sisters, each with constricted fields with preserved central vision. We identified one pathogenic POMGNT1 variant (c.751 + 1G > A) and one likely pathogenic variant (c.1010T > C p.Ile337Thr) in all three sisters. A thorough family history and examination of the siblings with genotyping might have led to an earlier diagnosis of retinal inherited disease and avoidance of immunomodulatory treatment in the oldest sibling. [ABSTRACT FROM AUTHOR]