Clinical Evidence for the Importance of the Wild-Type PRPF31 Allele in the Phenotypic Expression of RP11

• Published in: Genes Vol. 12; no. 6; p. 915
• Main Authors: Roshandel, Danial, Thompson, Jennifer A., Heath Jeffery, Rachael C., Zhang, Dan, Lamey, Tina M., McLaren, Terri L., De Roach, John N., McLenachan, Samuel, Mackey, David A., Chen, Fred K.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 14.06.2021; MDPI
• Subjects: Acuity; Age; Alleles; Children; Copy number; Diabetic retinopathy; Gene loci; Genomes; Genotyping; Mutation; Phenotypes; Phenotypic variations; Retinitis; Retinitis pigmentosa; Retinopathy; United States > US; Germany
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12060915

PRPF31-associated retinopathy (RP11) is a common form of autosomal dominant retinitis pigmentosa (adRP) that exhibits wide variation in phenotype ranging from non-penetrance to early-onset RP. Herein, we report inter-familial and intra-familial variation in the natural history of RP11 using multimodal imaging and microperimetry. Patients were recruited prospectively. The age of symptom onset, best-corrected visual acuity, microperimetry mean sensitivity (MS), residual ellipsoid zone span and hyperautofluorescent ring area were recorded. Genotyping was performed using targeted next-generation and Sanger sequencing and copy number variant analysis. PRPF31 mutations were found in 14 individuals from seven unrelated families. Four disease patterns were observed: (A) childhood onset with rapid progression (N = 4), (B) adult-onset with rapid progression (N = 4), (C) adult-onset with slow progression (N = 4) and (D) non-penetrance (N = 2). Four different patterns were observed in a family harbouring c.267del; patterns B, C and D were observed in a family with c.772_773delins16 and patterns A, B and C were observed in 3 unrelated individuals with large deletions. Our findings suggest that the RP11 phenotype may be related to the wild-type PRPF31 allele rather than the type of mutation. Further studies that correlate in vitro wild-type PRPF31 allele expression level with the disease patterns are required to investigate this association.