RP1-associated recessive retinitis pigmentosa caused by paternal uniparental disomy

We report on a patient with a juvenile-onset inherited retinal degeneration (IRD) associated with homozygous RP1 mutations inherited by uniparental disomy (UPD).

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).

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.

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.