The PRPH2 gene encodes a protein, Peripherin 2, that is important for the proper structure of the photoreceptor outer segment. It assembles into homo-tetramers and locates in the rim regions of the rhodopsin containing disks/lamellae of the photoreceptor outer segments, where it seems to stabilize structure by helping to maintain the curvature of the outer segment rim. This gene also forms hetero-tetramers with another highly homologous rod outer segment 1 (ROM1) protein.
Mutations in the PRPH2 gene impair protein function, thereby causing different retinal disorders, leading to progressive vision loss
The human PRPH2 gene is located on chromosome 6p21.1 and is composed of five exons. The protein product encoded by the gene is made up of 346 amino acids. PRPH2 belongs to the tertraspanin family of proteins, members of which are characterized by the presence of four hydrophobic transmembrane domains. The protein contains a large, conserved region, called the D2 intradiscal region, which plays an important role in the PRPH2 complex assembly necessary for disc formation and stabilization.
Khan et al. (2015) studied three consanguineous families confirmed to have children affected with non-syndromic early childhood onset retinal dysfunction. All patients in these families underwent diagnostic next generation sequencing (NGS) of a panel of all retinal dystrophy genes. The single affected patient in the first family was found to be homozygous for a novel PRPH2 mutation (c.497G>A; p.Cys166Tyr) and both parents were confirmed as heterozygous carriers. Two affected siblings in the second family were confirmed to be homozygous for the mutation c.136C>T (p.Arg46*) in the same gene. This mutation has been associated with a diagnosis of Leber congenital amaurosis. The heterozygous parents had mild myopia. The two affected siblings in the third family were found to be homozygous for the same PRPH2 mutation found in Family 1. Their mother had noticed loss of vision in her right eye, and was confirmed to be heterozygous for the familial PRPH2 mutation. The authors concluded that bi-allelic PRPH2 mutations caused a distinct Leber congenital amaurosis phenotype in infancy, with affected adults having prominent maculopathy. The heterozygous parents could be asymptomatic but have clinically obvious macular phenotypes with or without peripheral retinal findings