Variable clinical course of retinitis pigmentosa patients with RPE65 gene mutations

This retrospective observational study characterized the clinical features and visual function of early- and later-onset retinitis pigmentosa (RP) caused by biallelic variants in the RPE65 gene ( RPE65 -RP). Nine genetically confirmed patients (seven unrelated individuals and one pair of siblings) from four Japanese institutions were included. Clinical data, including best-corrected visual acuity (BCVA), fundus and autofluorescence imaging, optical coherence tomography, Goldmann perimetry, and electroretinogram, were reviewed. Most patients developed symptoms in early childhood (2–7 years), while one showed adult-onset disease. No patients showed nystagmus, and five had BCVA of 20/40 or better at some point by either history or measurement. However, seven patients eventually experienced BCVA of 20/250 or worse in at least one eye. Two patients with compound heterozygous variants, i.e., c.1543C > T (p.Arg515Trp) and c.683A > C (p.Gln228Pro), retained good vision and wider residual ellipsoid zone and visual field. All patients showed retinal degeneration consistent with RP and non-detectable electroretinogram responses. RPE65 -RP resulted in severe visual handicap by early adulthood in many cases. These findings present phenotypic features and variability in RPE65 -RP.