The spectrum of retinal dystrophies caused by mutations in the peripherin/RDS gene

Peripherin/rds is an integral membrane glycoprotein, mainly located in the rod and cone outer segments. The relevance of this protein to photoreceptor outer segment morphology was first demonstrated in retinal degeneration slow (rds) mice. Thus far, over 90 human peripherin/RDS gene mutations have been identified. These mutations have been associated with a variety of retinal dystrophies, in which there is a remarkable inter- and intrafamilial variation of the retinal phenotype. In this paper, we discuss the characteristics of the peripherin/RDS gene and its protein product. An overview is presented of the broad spectrum of clinical phenotypes caused by human peripherin/RDS gene mutations, ranging from various macular dystrophies to widespread forms of retinal dystrophy such as retinitis pigmentosa. Finally, we review the proposed genotype–phenotype correlation and the pathophysiologic mechanisms underlying this group of retinal dystrophies.