Identification of two novel PRPF31 mutations in Chinese families with non‐syndromic autosomal dominant retinitis pigmentosa

Background Retinitis pigmentosa is a heterogeneous group of inherited retinal diseases leading to progressive vision loss. It has been estimated that the etiology is still unclear in 22%‐40% of cases, indicating that many novel pathogenic variations related to RP remain unidentified in many patients. In this study, our aim was to investigate the disease‐causing variants and function of the variants in two Chinese families with non‐syndromic autosomal dominant retinitis pigmentosa (adRP). Methods Clinical data and peripheral blood DNA samples were collected. Whole exome sequencing (WES) was conducted to screen for variations. Then, the expression of green fluorescent protein (GFP)‐fused wild‐type PRPF31 protein and its variants was evaluated via western blotting and GFP fluorescence detection in vitro . Results Two novel heterozygous variants of PRPF31 (NM_015629.4): c.855+5G>A and c.849_855del (p.Pro284Ilefs*35) were identified respectively in two families. The variant c.855+5G>A is co‐segregated with the disease in adRP‐01 family. The pedigree analysis result for c.849_855del (p. Pro284Ilefs*35) shows an inheritance pattern with incomplete penetrance for adRP‐02 family. The RT‐PCR analysis shows the PRPF31 gene c.855+5G>A leading to the missing from the 997th to the 1405th positions of the PRPF31 gene (NM_015629.4) cDNA. The expressions of the mutant GFP‐fused PRPF31 protein were not detected in HEK293 cells or Cos7 cells via western blotting and immunofluorescence. Conclusions Our findings identified two novel variants in PRPF31 in two Chinese families with adRP, expanding the mutational spectrum of this gene. Functional analysis reveals that these variants lead to the truncation of the PRPF31 protein.