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. 2023 Jun 30;24(13):10895.
doi: 10.3390/ijms241310895.

Clinical Characteristics and Genetic Variants of a Large Cohort of Patients with Retinitis Pigmentosa Using Multimodal Imaging and Next Generation Sequencing

Richard Sather 3rd  1 , Jacie Ihinger  1 , Michael Simmons  1 , Tahsin Khundkar  1 , Glenn P Lobo  1 , Sandra R Montezuma  1
Affiliations

Clinical Characteristics and Genetic Variants of a Large Cohort of Patients with Retinitis Pigmentosa Using Multimodal Imaging and Next Generation Sequencing

Richard Sather 3rd et al. Int J Mol Sci. .

Abstract

This retrospective study identifies patients with RP at the Inherited Retinal Disease Clinic at the University of Minnesota (UMN)/M Health System who had genetic testing via next generation sequencing. A database was curated to record history and examination, genetic findings, and ocular imaging. Causative pathogenic and likely pathogenic variants were recorded. Disease status was further characterized by ocular coherence tomography (OCT) and fundus autofluorescence (AF). Our study cohort included a total of 199 patients evaluated between 1 May 2015-5 August 2022. The cohort included 151 patients with non-syndromic RP and 48 with syndromic RP. Presenting symptoms included nyctalopia (85.4%) photosensitivity/hemeralopia (60.5%), and decreased color vision (55.8%). On average, 38.9% had visual acuity of worse than 20/80. Ellipsoid zone band width on OCT scan of less than 1500 μm was noted in 73.6%. Ninety-nine percent had fundus autofluorescence (AF) findings of a hypo- or hyper-fluorescent ring within the macula and/or peripheral hypo-AF. Of the 127 subjects who underwent genetic testing, a diagnostic pathogenic and/or likely pathogenic variant was identified in 67 (52.8%) patients-33.3% of syndromic RP and 66.6% of non-syndromic RP patients had a diagnostic gene variant identified. It was found that 23.6% of the cohort had negative genetic testing results or only variants of uncertain significance identified, which were deemed as non-diagnostic. We concluded that patients with RP often present with advanced disease. In our population, next generation sequencing panels identified a genotype consistent with the exam in just over half the patients. Additional work will be needed to identify the underlying genetic etiology for the remainder.

Keywords: fundus autofluorescence; genetic testing; inheritance patterns; next generation sequencing; ocular coherence tomography; retinitis pigmentosa.

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Conflict of interest statement

We, as a team, do not have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real conflict of interest in the context of the subject of this case report.

Figures

Figure 1
Figure 1
Criteria for diagnostic imaging modalities utilized for the patient cohort. (A) example parameter measurement of patient OCT EZ (ellipsoid zone) bandwidth interpretation. (B) Example criteria for FAF (fundus autofluorescence) imaging. Macula hypo/hyper-AF and peripheral hypo-AF.
Figure 2
Figure 2
Detailed summary of the patient cohort who underwent genetic testing.
Figure 3
Figure 3
Distribution of causative RP genes identified in the patient cohort. * The ‘Other’ category includes cases in which only a single patient had diagnostic findings in a particular gene. Please refer to Figure 2 for the full list.
See this image and copyright information in PMC

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