A 21-year-old male with no history of nyctalopia or parental consanguinity presented to the vitreoretinal service at King Khaled Eye Specialist Hospital with a 1-week decrease of vision in the right eye. The patient had no known systemic disorders. On ophthalmic examination, best-corrected visual acuities (BCVAs) were hand motion in the right eye and 20/20 in the left eye. On anterior segment examination, there were 3+ cells in the right eye and the left eye was unremarkable.
Fundus examination indicated 3+ vitreous cells in the right eye, obscuring the view of the retina. In the left eye, bone spicules were present and were mostly condensed around attenuated retinal blood vessels. Optic disc or vascular leakage was not clearly evident on fundus fluorescein angiography (FFA) due to the hazy media from the vitreous haze. Systemic workup was negative for complete blood count, renal function test, liver function test, chest computed tomography, fluorescent treponemal antibody absorbed, purified protein derivative, and tuberculosis-quantiferon gold test. Erythrocyte sedimentation rate, C-reactive protein, angiotensin-converting enzyme, antinuclear antibodies, and antineutrophil cytoplasmic antibodies were within the normal limits.
The patient was managed with topical steroids four times daily on a weekly taper. Two weeks after initiating therapy, BCVA had improved to 20/30 in the right eye with few vitreous cells and more densely distributed bone spicules than in the left eye [Figure 1a and b]. Fundus autofluorescence indicated hypofluorescent areas corresponding to bone spicules and hyperfluorescent rings in the macular region in both eyes [Figure 1c and d]. Spectral-domain optical coherence tomography indicated photoreceptor loss beyond the macular area bilaterally and a few vitreous cells in the right eye [Figure 1e and f]. Fundus full-field electroretinogram indicated profoundly reduced scotopic and photopic responses in both eyes with a greater reduction in the right eye [Figure 2]. Over 6 months follow-up, the patient maintained 20/20 vision with no recurrence of inflammation.
Whole exome sequencing was performed at Bioscientia, Ingelheim, Germany, revealed a novel homozygous c. 3061-6_3061-3del (NM_006445.3) mutation in premessenger RNA (mRNA) processing factor 8 (PRPF8; MIM 600059). This mutation leads to significant alteration of the acceptor 3' splice site based on in silico predictions using in-house prediction programs. The mutation was verified with polymerase chain reaction (PCR) followed by conventional Sanger sequencing. Allele frequency of this variant has not been documented in the normal population (GnomAD v2.1.1 controls; accessed on July 17, 2020). PRPF8 plays an integral role in pre-mRNA splicing and processing of intron-containing transcripts. Pathogenic variants in PRPF8 affect spliceosome assembly and function through interaction with SNRNP200, are present in autosomal dominant retinitis pigmentosa (ADRP).