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Background: We report on a patient with a juvenile-onset inherited retinal degeneration (IRD) associated with homozygous RP1 mutations inherited by uniparental disomy (UPD)., Material and Methods: A 6-year-old healthy girl failed school vision screening and was diagnosed with a bull's eye maculopathy. She underwent complete ophthalmic examination, full-field electroretinograms (ERG), kinetic fields, full-field sensitivity testing (FST), and retinal imaging with spectral domain optical coherence tomography (SD-OCT) and near-infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF)., Results: Visual acuities were relatively preserved (20/30+). There was subtle foveal depigmentation but an otherwise normal fundus examination. SD-OCT revealed a relatively preserved fovea with thinning of the photoreceptor outer nuclear layer with increasing distance from the foveal center coinciding with marked attenuation of the NIR and less marked loss of the SW-FAF signal. ERGs were non-detectable. Kinetic visual fields were generally full to large (V-4e) target but constricted to ~10°of eccentricity to I-4e stimuli. Dark-adapted thresholds by FST were rod-mediated and elevated by ~2 log units. Homozygous pathogenic mutations in RP1 (c.1720_1721del; p.Ser574Asnfs*8) were identified. Family member testing revealed father and siblings to be unaffected carriers; the mother carried wild-type alleles. Further testing suggested UPD of chromosome 8., Conclusion: This report adds support to UPD as a mechanism of inheritance in IRDs and stresses the importance of familial testing for genetic diagnosis and counseling. Consistent with earlier descriptions of autosomal recessive RP1 -IRDs our patient showed an early rod and cone photoreceptor degeneration.

Purpose: To describe in detail the phenotype of a patient with compound heterozygous mutations in ZNF408 and an adult-onset pigmentary retinopathy rather than familial exudative vitreoretinopathy as expected with heterozygous mutations in this gene., Methods: A 70-year-old male presented with a pigmentary retinopathy, which prompted a genetic evaluation that revealed two variants in trans in the ZNF408 gene. He underwent an ophthalmic examination, kinetic fields, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, wide-angle fluorescein angiography and near-infrared imaging., Results: Visual acuity was 20/20 for both eyes. Fundus examination showed epiretinal membrane, vascular attenuation and peripheral bone spicule pigmentation in both eyes. Fluorescein angiography showed no vascular anomalies in both eyes. Fundus autofluorescence showed a preserved island of fundus autofluorescence centrally. Visual field by kinetic perimetry (V-4e stimulus) showed generalized constriction to 40 degrees of eccentricity and by an I-4e target showed generalized constriction to 10 degrees of eccentricity. ERG showed detectable but reduced cone-mediated responses. SD-OCT demonstrated preserved outer nuclear layer thickness centrally, which decreased with eccentricity. Static perimetry showed substantial rod and cone sensitivities centrally that declined with eccentricity. A next-generation sequencing panel revealed bi-allelic variants (p.Arg567Ter; c.1699C > T and p.Leu566His; c.1697 T > A) in the ZNF408 gene., Conclusions: ZNF408-associated retinal dystrophies can present with predominantly retinal findings and should be considered in the differential diagnosis of retinitis pigmentosa. Our study revealed a novel variant p.L566H, which to our knowledge has not previously been reported., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)