A novel homozygous missense mutation in the RPE65 gene in an Iranian family with retinitis pigmentosa

Hereditary retinal dystrophies such as retinitis pigmentosa (RP) are genetically and phenotypically heterogeneous and result in total blindness. One of the key genes causing RP is RPE65. In 2017, a gene therapy drug, voretigene neparvovec-rzyl, for RP associated with RPE65 mutations, received Food and Drug Administration approval. So, identification of RPE65 gene mutations in affected patients which may be amenable to genetic treatment is critical. Here, we examine three related Iranian patients with RP which have not been previously described in the population. Whole exome sequencing (WES) using next-generation Illumina sequencing was utilized to identify the disease-causing mutation in the proband. Subsequently, Sanger sequencing was performed to confirm the identified mutation in the patients and their family members. Finally, the possible effect of the reported mutation on the target protein was also evaluated using bioinformatics tools. WES identified a novel homozygous missense mutation c.T170C: p.F57S in exon 3 of the RPE65 gene. Sanger sequencing confirmed the mutation found in the patients and their healthy family members. This mutation segregated with the autosomal recessive inheritance pattern of RP disorder. Furthermore, the pathogenic nature of the identified mutation was confirmed by in silico approaches and genotype-phenotype correlation analysis. Our findings revealed a novel missense mutation c.T170C: p.F57S in the RPE65 gene and could expand the pathogenic mutations spectrum of the RPE65 gene. Additionally, such studies can aid to conduct genetic counseling, prenatal diagnosis, clinical management and even genetic treatment more accurately for all affected patients with RPE65 gene mutations.