Abstract
Purpose :
Attention to genetic testing for patients with inherited retinal diseases (IRD) has increased among patients and clinicians due to significant advances in genomics and gene therapy. However, routine genetic testing for clinically diagnosed IRD is not currently common practice for reasons including extra cost and clinicians’ limited familiarity with its utility. In the current study, we share our experience in genetic testing of clinically diagnosed IRD patients using no-charge panel genetic testing.
Methods :
Retrospective case analysis was performed of patients clinically diagnosed with IRD, who elected to undergo molecular genetic testing from 2019 to 2020 at a single academic center. Testing was performed with a saliva kit, in which 248 genes were assayed from a kit provided by Invitae (San Francisco, CA, USA) and sponsored by Spark Therapeutics (Philadelphia, PA, USA).
Results :
Forty-seven patients (M 21: F 26) were included. The following diagnoses were represented:
1) photoreceptor disease (30/47, 63.8%), including retinitis pigmentosa (RP) (21/47, 44.7%), cone and cone-rod dystrophy (4/47, 8.5%), and syndromic RP (5/47, 10.6%); 2) macular diseases (11/47, 23.4%), including Stargardt’s (5/47, 10.6%); and 3) other diseases (6/47, 12.8%), including choroideremia (3/47, 6.4%) and X-linked retinoschisis (2/47, 4.3%). Disease-causing genotypes were identified in 46.8% of patients (22/47), 42.3% in RP (11/26), 80% in Stargardt’s (4/5), and 100% in choroideremia (3/3). Undetermined genotypes in 53.2% (25/47) patients were due to identifying either one recessive pathogenic mutation or multiple variants of unknown significance (VUS). Common VUS identified in our cohort were USHA2A(7), TUBGCP6 (6), CDH23(6), FSCN2(6), PCDH15(6), WHRN(6), ABCA4(5), and EYS(5).
Conclusions :
Here, we report the results of currently available no-charge panel genetic testing to explore its utility in an established IRD clinic setting. We further plan to examine how testing utility may change depending on demographics or in phenotypic subdivisions in our cohort. Further studies interpreting the frequency of VUS and whether and how VUS are related to disease in our cohort will be pursued. In doing so, we aim to provide early guidance for retina specialists on the value of genetic testing in the practical management of IRDs.
This is a 2021 ARVO Annual Meeting abstract.