Abstract
Purpose :
Purpose: Diagnostic yield of genetic testing in inherited retinal disease (IRD) has been reported between 56-76%. Studies have focused on the yield of panel testing, copy number variant testing, or broad-based sequencing, such as exome sequencing (ES) or genome sequencing (GS). Data are limited on the utility of broad-based testing for patients after inconclusive targeted IRD panel testing. We posit that ES or GS is warranted after an inconclusive panel.
Methods :
Methods: We performed a retrospective analysis on 191 patients who underwent genetic testing for IRDs between 12-12-07 and 9-29-23 at Mayo Clinic. Cases were grouped by testing strategy as targeted IRD panel testing only, ES after panel and GS after panel. Genetic testing results across these groups were categorized as either unsolved, solved, or likely solved for retinal phenotype. The percentage of conclusive cases were analyzed by two-tailed Chi-square testing to determine differences between two groups.
Results :
Results: Combined all testing strategies had 113 out of the total of 191 cases solved or likely solved (59.2%). Panel testing only was performed for 134 patients with 100 being solved or likely solved (74.6%). Twenty-seven patients had ES post inconclusive panel with seven having diagnostic variants (25.9%), increasing yield from 62.1% (100/161) to 66.5% (107/161). Twenty-five individuals had GS after inconclusive panel with three being solved or likely solved (12.0%), increasing yield from 62.9% (100/159) to 64.8% (103/159). GS after inconclusive ES yielded no additional solved cases (0/6). Collectively, broad-based sequencing after an inconclusive IRD panel had a 19.2% clinical yield (10/52) with 10 additional solved cases, increasing diagnostic yield from 53.7% (100/186) to 59.1% (110/186) for all patients obtaining an IRD panel (5.4% increase). Five patients had ES without a previous panel; three were solved (60.0%).
Conclusions :
Conclusion: Exome or genome sequencing increases diagnostic yield for individuals with inconclusive IRD panel testing. In this cohort, 10 patients had genetic etiology confirmation with either ES or GS that was not detected with targeted IRD panel testing alone. This increase in yield warrants the consideration of broad-based testing after inconclusive targeted IRD panel testing.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.