EVIDENCE THAT THE PENETRANCE OF MUTATIONS AT THE RP11 LOCUS CAUSING DOMINANT RETINITIS-PIGMENTOSA IS INFLUENCED BY A GENE LINKED TO THE HOMOLOGOUS RP11 ALLELE

A subset of families with autosomal dominant retinitis pigmentosa (RP) display reduced penetrance with some asymptomatic gene carriers showi ng no retinal abnormalities by ophthalmic examination or by electroret inography. Here we describe a study of three families with reduced-pen etrance RP. In all three families the disease gene appears to be linke d to chromosome 19q13.4, the region containing the RP11 locus, as defi ned by previously reported linkage studies based on five other reduced -penetrance families. Meiotic recombinants in one of the newly identif ied RP11 families and in two of the previously reported families serve to restrict the disease locus to a 6-cM region bounded by markers D19 S572 and D19S926. We also compared the disease status of RP11 carriers with the segregation of microsatellite alleles within 19q13.4 from th e noncarrier parents in the newly reported and the previously reported families. The results support the hypothesis that wild-type alleles a t the RP11 locus or at a closely linked locus inherited from the nonca rrier parents are a major factor influencing the penetrance of pathoge nic alleles at this locus.