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Teja Chemudupati, Young Joo Sun, Jing Yang, Benjamin Ng, Vinit B Mahajan; Novel PRPF31 gene loss of function for retinitis pigmentosa 11. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3037.
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© ARVO (1962-2015); The Authors (2016-present)
This study reports the ophthalmic and genetic findings of a patient with autosomal dominant retinitis pigmentosa (adRP) subtype RP11 caused by a novel Pre-mRNA Processing Factor 31 (PRPF31) heterozygous mutation.
A patient consent allowing researchers to store annotated health information and perform retrospective chart review was approved by Stanford University’s Institutional Review Board. Following informed consent, a 22-year-old male reporting fluctuating vision underwent comprehensive ophthalmic examinations including visual acuity measurements, dilated fundus imaging, electroretinography (ERG), and optical coherence tomography (OCT). To determine the genetic etiology, sequence analysis using the Blueprint Genetics (BpG) Retinal Dystrophy Panel was performed. The nucleotide sequence of the identified mutation was manually prepared from PRPF31 wild-type mRNA sequence and translated to amino acid sequence by ExPASy translate tool. The wild-type PRPF31 structure was extracted from the cryo-EM structure of a pre-catalytic human spliceosomal B complex and the structural model was presented as a figure using Pymol.
Fundus examination revealed pigmentary changes in the temporal periphery, vitreous syneresis, and epiretinal membrane OU. Fundus autofluorescence demonstrated mid-periphery hypoautofluorescence and a hyperautofluoresence ring in macula OU. OCT imaging of the macula OU showed epiretinal membrane. Compared to a normal control, scotopic and photopic ERG demonstrated no recognizable response or signals recorded in rod or cone photoreceptor cell response indicating pervasive damage. Genetic testing via BpG panel revealed a novel heterozygous mutation (c.358_361del, p. Lys120Aspfs*77) in the gene encoding PRPF31 predicted to result in complete knockout of function at the protein level, destabilizing the pre-catalytic spliceosome (complex B).
Our novel heterozygous mutant is found at one of the earliest points of PRPF31 among the reported pathogenic genetic variants and has complete knockout function, resulting in a protein truncated before the snoRNA binding site region of PRPF31 and no nuclear localization signal (NLS). These predicted changes caused by our reported variant in context with other known mutations expand the understanding of the disease mechanism in RP11 haploinsufficiency.
This is a 2020 ARVO Annual Meeting abstract.
Fig 1. Ophthalmic Imaging
Fig 2. PRPF31 Modeling
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