A Description of the Yield of Genetic Reinvestigation in Patients with Inherited Retinal Dystrophies and Previous Inconclusive Genetic Testing

In the present era of evolving gene-based therapies for inherited retinal dystrophies (IRDs), it has become increasingly important to verify genotype in every case, identify all subjects eligible treatment. Moreover, combined insight concerning phenotypes and genotypes is crucial improved understanding thevisual impairment, prognosis, inheritance. The objective this study was investigate what extent renewed comprehensive genetic testing patients diagnosed with IRD but previously inconclusive DNA test results can genotype, if confirmation an impact on clinical picture, and, describe spectrum encountered a Swedish cohort. included 279 from retinitis pigmentosa research registry (comprising diagnosis within whole spectrum), hosted at Department Ophthalmology, Skåne University hospital, Sweden. had already been evaluated electrophysiology other tests, e.g., visual acuity, Goldmann perimetry, fundus imaging first visit, sometime between 1988–2015 previous—in many cases, multiple—genetic testing, performed 1995 2020 inconclusive. All were aged 0–25 years time their visit. Renewed using next generation sequencing (NGS) panel including 322 genes (Blueprint Genetics). Class 5 4 variants, according ACMG guidelines, considered pathogenic. Of samples tested, confirmed determined 182 (65%). cohort genetically heterogenous, 65 different genes. most prevailing ABCA4 (16.5%), RPGR (6%), CEP290 RS1 (5.5%). Other prevalent CACNA1F (3%), PROM1 CHM NYX (3%). 7% there discrepancy made based phenotypical or genotypical findings alone. To conclude, repeated DNA-analysis beneficial also tested our ability genotype–phenotype association increasing how impairment manifests, inheritance pattern. widely available method could additional future therapies.