Abstract
Purpose :
Recent promising results in the use of gene therapy for inherited retinal disease (IRD) have prompted the implementation of genetic testing to evaluate for the presence of mutations in relevant genes. This study reports the findings following a retrospective review of genetic testing results in patients diagnosed with IRD. Subsequent analysis of data will provide insight into the relative frequency of pathogenic retina-associated gene mutations within Chicago, IL.
Methods :
A query was made of the Illinois Retina Associates (IRA) and Rush University Eye Center Physicians (RU ECP) databases to identify patients with diagnoses representing IRD as identified by the following ICD-10-CM codes: pigmentary retinal disorder (H35.52), unspecified hereditary retinal dystrophy (H35.50), and other dystrophies primary involving the sensory retina (H35.53). Eligibility was confirmed via chart review. Patients were included if a prior diagnosis of IRD was present and associated with pending or returned genetic testing results. After confirming eligibility, the following de-identified data was entered into the study database: medical record number, age, gender, race, clinical diagnosis, genetic testing service, genetic panel used, and results.
Results :
487 patients at IRA and 49 at RUECP were identified as having appropriate codes between 1/1/2014 and 12/31/2020. 68 patients have been tested for retinal specific gene mutations through commercial genetic laboratories to date. 67 patients have testing resulted. 0/67 (0%) patients were positive for RPE 65. 49/67 (73%) patients had positive results of heterozygosity in at least one implicated gene. 54/67 (80%) patients had positive results of variants of unknown significance. Pathogenic variants were identified in 27 different genes, the most frequent being ABCA4, USH2A, and NR2E3 in decreasing order.
Conclusions :
ABCA4 and USH2A were idenitifed as the two most frequent implicated genes, consistent with previously published data. In contrast to prior publications, we found the third most frequent pathogenic variant to be NR2E3, which was previously reported as a rare cause of IRD. These contrasting findings suggest that additional analyses of IRD genetic testing results from large populations are required to provide those researching novel gene therapies with the target that will provide the greatest impact.
This is a 2021 ARVO Annual Meeting abstract.