Non-syndromic retinitis pigmentosa (RP) refers to a heterogeneous group of inherited retinal diseases (IRDs) characterized by night-blindness and development of tunnel vision followed by central vision involvement. To date, more than 80 genes have been identified as the cause of RP inherited in autosomal dominant, autosomal recessive, or X-linked patterns. Frequencies of each mutated genes related to RP can be various among the different populations. Here, we describe genetic analysis of twenty-four Iranian pedigrees with RP for identification of the causing genes and mutations.

We collected blood samples of 46 patients from 24 unrelated Iranian families diagnosed with different inheritance patterns of RP. Complete ophthalmic examinations were performed for the affected members of the families. Genomic DNA was extracted from peripheral blood leukocytes using the standard salting out method. We used a cost-effective targeted sequencing based on molecular inversion probes (MIPs) to sequence the coding regions of 108 non-syndromic IRD-associated genes. Subsequently, the candidate causing mutations were screened for segregation in the pedigrees by Sanger sequencing. The in silico bioinformatics tools were used to predict and score the deleterious effects of the novel identified nucleotide changes on the protein products.

Our study revealed RP causing mutations in 75% (18 from 24) of the studied families. Twenty different mutations in twelve genes were identified as the cause of disease in the families. Of these, 8 mutations (40%) were not been previously reported as disease-causing mutations. CRB1 was the most frequent causing gene in our cohort (22.2%) and ABCA4, USH2A and EYS genes were also more frequent than the other screened genes.

This study supports the genetic heterogeneity of RP in Iranian patients with special genes and mutations spectrum. We showed the used genetic testing for Iranian RP affected families is about 75% sensitive. Using a larger sample size and more investigation of the negative families for screened genes, we can design a clinically directed genetic panel for Iranian patients. This can increase sensitivity of the genetic strategy and be cost-effective for genetic counseling.