Identification of the RP1 and RP10 (IMPDH1) genes causing autosomal dominant RP.

Abstract

In a project begun more than 15 years ago we used linkage mapping and positional candidate gene cloning to identify two genes causing autosomal dominant retinitis pigmentosa (adRP). The genes are RP I, which maps to chromosome 8q12.1, and RP10 (IMPDH 1), which maps to 7g32.1. Although different families and different regions of the genome are involved, the studies were done in parallel because the methods used, and the underlying genetic concepts, are identical. Now that the genes have been identified, though, the functional properties of the two proteins are strikingly different, so divergent approaches are required to better understand the pathophysiology of mutations in each gene. This report is a summary of our current understanding of these two genes, contrastingthe similar approaches to identifying the genes and mutations with the dissimilar strategies for functional analysis. In microcosm, this serves as a reminder that retinal disease genes associated with similar clinical phenotypes may have very different biological roles.