Frequency of RPE65 Gene Mutation in Patients with Hereditary Retinal Dystrophy

Abstract

Objectives: Hereditary retinal dystrophies are a rare group of diseases which are heterogeneous in genotype and phenotype and result in total blindness. One of the genetic defects that cause hereditary retinal dystrophy is mutation of the RPE65 gene. Genetic therapy studies in hereditary retinal dystrophies have increased in number recently, and important developments have been reported in these studies. Voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), a gene therapy drug for retinal dystrophy associated with RPE65 mutation, received Food and Drug Administration approval in 2017. This study aimed to investigate the frequency and clinical findings of patients with RPE65 gene defects, which may be amenable to genetic treatment.

Materials and methods: The data of patients diagnosed with hereditary retinal dystrophy who were followed up between 2017 and 2021 were retrospectively reviewed. Of these, 460 patients with genetic analysis results were included in the study. The clinical findings of patients with homozygous (biallelic) RPE65 mutation were screened.

Results: RPE65 homozygous gene mutation was detected in only 11 of 460 cases (2.39%). Genetic results of the cases were presented in detail. The inheritance patterns of the cases were autosomal recessive. The demographic data and clinical findings were defined.

Conclusion: RPE65 gene mutation is a very rare disorder. Genetic screening has gained importance with the emergence of gene therapy alternatives. New treatment methods are promising in cases for which there was no chance of a cure to date.

Keywords: RPE65 gene; gene therapy; hereditary retinal dystrophy.

Figure 1

In patient 5, peripheral bone spicules, optic disc pallor, widespread retinal atrophy, and vessel narrowing were observed in right and left fundus photographs (a and b). Macular thinning on optical coherence tomography (c and d) and visual field narrowing (e and f) were also apparent

Figure 2

Olgu 5’e ait optik koherens tomografi görüntüsünde santral maküla kalınlığı ve retinada dış segment iç segment bileşkesinin tamamen bozulduğu, yaygın dejenere bir retina görülmektedir

Figure 3

In patient 5, optical coherence tomography showed an extensive retinal degeneration with severe central macular thinning and complete disruption of the retinal outer segment/inner segment junction