Objective: We are reporting a new variation RPE65 pG140E, c419G>A as a pathogenic variant. An apparently asymptomatic male with fine bright white dots in macula and generalized constricted visual fields.
Introduction: The RPE65 protein is the source of isomerohrydrolase activity (conversion of all-trans retinyl ester to 11-cis retinol) in the retinal pigment epithelium. The characterization of RPE65 gene was first described by Nicoletti et al. 1995, which encodes the abundant 61-kD protein in Retinal Pigment Epithelium (RPE) monolayer simple epithelium opposed to the outer surface of the retina photoreceptor cells. RPE works in metabolism in outer layers that are essential to continued maintenance of the photoreceptor cells, including vision functionality as visual cycle photoreceptor recycling and outer segment phagocytosis. Among functions are 1) Phagocytizes periodically the tips of outer segments, process whose defects leads to retinal degeneration, 2) RPE65 is site of many enzymes involved in retinoid metabolism, including retinyl ester synthetase and 3) Lecithin: retinol acyltranferase, 4) Retinyl ester hydrolase, 5) Retinol isomerase, 6) 11-cis retinol deshidrogenase as well as 7) Rpe-/retina-specific cellular retinaldehyde binding protein, 8) ion transport 9) digestion of phagosomes and 10) detoxification of photoreceptors by products, and therefore all type of variations might develop a visual change.
Methodology: Ocular, visual fields, autofluoresce, OCT, genetic exam.
Results: We are reporting an heterozygous individual for a maternal- pathogenic variant (c.292_311del20) and a paternal-variant (c.419 G>A) of uncertain significance in RPE65 gene reported until 2015, however this variant should be reported as pathogenic. The combination of c419G>A (new variation, not previously reported from father) and p.I98HfsX26, c.292_311del20 (known pathogenic variation- from mother) in a 3 years old, makes a pathogenic phenotype not reported previously.
Keywords: Retinal Pigment Epithelium (RPE), Photoreceptor cells, RPE65 mutation.