Abstract
Purpose :
Genetic factors have a major influence on variable expressivity in gene-phenotype relationships. This study aims to identify potential pathogenic gene variants in patients diagnosed with syndromic and non-syndromic retinitis pigmentosa (RP). A genotype-phenotype correlation is important as there are current and future therapies catered to the genetic inheritance and physical expression for this disease.
Methods :
This retrospective series identifies patients with RP who had genetic testing using next generation sequencing panel at the UMN. A database was created to record history and examination, genetic report, and diagnostic imaging. Causative pathogenic genes were recorded. Patient disease status was further characterized by ocular coherence tomography (OCT) and fundus autofluorescence (AF).
Results :
200 patients were included consisting of 154 non-syndromic and 46 syndromic RP. Results were only recorded if stated in the patient’s chart. 42.8% of patients first noted eye symptoms before the age of 10. 56.6% had a family history of retinal dystrophy. Presenting symptoms included 85.4% with nyctalopia, 60.2% with photosensitivity/hemeralopia, and 54.7% with decreased color vision measured by the Ishihara’s test. On average, 38.5% had visual acuity worse than 20/80. 92.4% had evidence of visual field loss. Ellipsoid zone width on the fovea OCT scan of less than 1500 μm was noted in 73.8%. Approximately 99.0% presented with Fundus AF findings of either macula hypo/hyper AF ring and/or peripheral hypo-AF. The genetic report analysis showed the largest contributed RP genetic finding was VUS at 68.7%. The top identifiable pathogenic variants included USH2A (14.3%), RPGR (7.5%), MYO7A (6.8%), EYS (4.1%), and RP1 (3.4%). 11 patients had X-linked RP, all with RPGR mutation. 13 patients had autosomal dominant RP, including 5 with RP1 mutation and a family of 4 patients with PRPH2 mutation.
Conclusions :
The results demonstrated that patients within the UMN are often evaluated for their RP in advanced disease independent of the genetic result. VUS comprised most of the genetic findings. This suggests the need to find either a more encompassing genetic analysis to account for the numerous RP genes and the diversity of our patients or promote testing for other affected RP family members to determine if the VUS is pathogenic.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.