PRPH2 (OMIM 179605) gene encodes a transmembrane glycoprotein named peripherin2 that also known as RDS, retinal degeneration slow. This glycoprotein has a key role in proper organization of rod and cone photoreceptor outer segments and thereby in vision process. This gene has been introduced as cause of various types of inherited retinal dystrophies. Here, we describe genetic analysis of an Iranian family presenting different retinal manifestations among the affected patients.

The parents of the family are first cousins and both of them are affected. They have two affected daughters, but one of them has more severe phenotype than her parents and her sister. The inheritance pattern seems to be ambiguous. Complete ophthalmic examinations were performed for the affected individuals. Genomic DNA was extracted from peripheral blood leukocytes of all family members using the standard salting out method. We applied whole exome sequencing (WES) and bioinformatics analysis to characterize the causative mutation in the affected members of the family. The identified pathogenic variant was validated using Sanger sequencing.

Clinical findings suggest central areolar chorioretinal dystrophy as the most probable clinical diagnosis for the parents and one of their daughters and Leber congenital amaurosis (LCA) for the daughter with more severe phenotype. We found a nonsense mutation in PRPH2 (NM_000322: p.Gln239Ter). The parents and their daughter with central areolar chorioretinal dystrophy diagnosis were heterozygous for the identified variant and interestingly, the LCA affected daughter was homozygous for the mutation. P.Gln239Ter mutation has been known as “Pathogenic” (https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs61755814). Segregation analysis of the variant with DNA samples of available family members confirms the probability of the pathogenicity of the mutation.

Mutation in PRPH2 gene is a relevant finding for central areolar chorioretinal dystrophy in autosomal dominant mode of inheritance and the more severe phenotype of one of the affected daughters is compatible with homozygous status of the allele for her. This study is the second report for the role of PRPH2 in LCA pathogenesis in the world and show two different inheritance patterns of two different types of inherited retinal dystrophies causing by PRPH2 in a single family.