Genetic testing results of retinal dystrophies in a diverse population: impact of race and ethnicity.

Abstract

Introduction: Due to the recent advent of gene-targeted retinal therapies, the clinical value of high-yield genetic testing for inherited retinal dystrophies (IRDs) has increased considerably. However, diagnostic yield is limited by the reported patient populations in allele frequency databases. This study aimed to determine the effect of race and ethnicity on diagnostic yield in IRDs.

Methods: Retrospective review of individuals with suspected IRD based on clinical findings or diagnosis of associated syndrome who underwent genetic testing between 2009 and 2021. Self-reported race and ethnicity, ophthalmic examination findings, ERG results, and genetic testing findings were collected and analyzed.

Results: In 93 individuals (90 families) with suspected IRD, the diagnostic yield was 72% (67 individuals). The rate of diagnostic yield was not significantly associated with family history, associated syndromes, age at testing, ERG results, or ophthalmic exam findings. Further, higher rates of positive diagnostic yield were not associated with more recent genetic testing. There was a trend toward differences in diagnostic yield between races (77% White, 65% Other, 64% Asian, 50% Black) and ratio of pathogenic/likely pathogenic (P/LP) variants to variants of unknown significance (46%:54% White, 36%:64% Other, 31%:69% Asian, 30%:70% Black).

Conclusions: Current genetic testing for IRDs trends toward higher diagnostic yield and identification of P/LP variants in patients identifying as White compared to other races. In order to prevent negative impacts on access to gene-targeted trials and treatments for non-White patients, wider genetic testing in diverse populations is required to create comprehensive catalogs of gene variants associated with IRDs.