Abstract
Purpose :
To investigate the spectrum and frequencies of genetic mutations in a cohort of patients with known or suspected retinal dystrophies and correlate them with phenotypical characteristics. Advances in next generation sequencing allow for patients to be tested in a cost-effective and rapid manner with identification of pathogenic mutations becoming more clinically relevant.
Methods :
A cohort of 29 patients seen in a general retina clinic with known or suspected retinal dystrophies were evaluated with a broad genetic testing panel comprising at least 248 genes (some patients had an updated panel of 293 genes) associated with the development of retinal dystrophies. Phenotypical characteristics were analyzed and related back to their associated genetic mutations to link disease features with genotypes.
Results :
Twenty-seven of 29 patients (93.1%) tested positive for a variant(s) in one or more of the genes tested. Fourteen of these patients (48.3%) tested positive for a pathogenic variant(s) in one or more of the genes tested. Thirteen patients (44.8%) were positive for genetic variants not yet associated with any particular retinal disorder (variants of unknown significance). Both patient groups had similar disease characteristics including reduced visual acuity, legal blindness, and dyschromatopsia. Two patients did not exhibit any specific genetic variants in the genes tested, but one of the two patients was discovered to have Klinefelter Syndrome (XXY).
Mutations were discovered in 69 of the 293 genes with ABCA4 and CA4 the most frequently mutated genes harboring pathogenic variants. GRM6 was the most frequently mutated gene of the variants of unknown significance.
Conclusions :
This study supports the utility of genetic testing with a broad screening panel in a cohort of patients who carry a clinical diagnosis of retinal dystrophy. In this cohort, a significant number of patients had a pathogenic genetic mutation or a variant identified.
This is a 2021 ARVO Annual Meeting abstract.