First symptoms occur in the second to third decade of life and patients become blind in their forties or fifties. The rod photoreceptors degenerate first, accompanied by night blindness. The disease progresses from the periphery towards the center of the retina. Consequently, the visual field of affected patients becomes more and more constricted. In advanced stages, cone photoreceptors die as well and the remaining visual acuity is very low or patients become legally blind.
Familial forms follow autosomal dominant, recessive and X-linked modes of inheritance.
More than 30 loci in the human genome were defined by genetic linkage studies and mutations in at least 15 different genes give rise to the RP phenotype. Some of the genes code for components of the phototransduction cascade, including rhodopsin, phosphodiesterase, and the cyclic nucleotide gated channel. Genetic linkage studies in X-linked families revealed at least five distinct loci. We have identified the respective genes by positional cloning and now focus on the analysis of disease-associated molecular mechanisms. One of the YACs detected an abnormal hybridization pattern in one out of 26 XLRP patients.