Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing

Abstract

Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia.

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

“…Notably, in the allelic Kufs A disease the retina is not affected and vision is normal. Recently, patients affected with isolated retinal degeneration (including retinitis pigmentosa) have been identified harboring biallelic CLN3 and CLN10 pathogenic variants ( 101 , 102 ).…”

Towards an Understanding of Retinal Diseases and Novel Treatment

“…A novel mutation in gene PRF1 that causes RP could be identified using family-based whole-exome sequencing. In a Taiwanese family, six snps candidates were identified as RP disease-causing variants, one the novel pathogenic variant PRF1 [ 17 ]. Variants in the RPE65 gene account for 1–6% of RP and 3–16% of Leber congenital amaurosis and early onset severe retinal dystrophy cases.…”