EVIDENCE FOR A MAJOR RETINITIS-PIGMENTOSA LOCUS ON 19Q13.4 (RP11), AND ASSOCIATION WITH A UNIQUE BIMODAL EXPRESSIVITY PHENOTYPE

Retinitis pigmentosa (RP) is the name given to a heterogeneous group o f retinal degenerations mapping to at least 16 loci. The autosomal dom inant form (adRP), accounting for similar to 25% of cases, can be caus ed by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus fo r adRP has previously been mapped to chromosome 19q13.4 in a large Eng lish family. This linkage has been independently confirmed in a Japane se family, and we now report three additional unrelated linked U.K. fa milies, suggesting that this is a major locus for RP. Linkage analysis in the U.K. families refines the RP11 interval to 5 cM between marker s D19S180 and AFMc001yb1. All linked families exhibit incomplete penet rance; some obligate gene carriers remain asymptomatic throughout thei r lives, whereas symptomatic individuals experience night blindness an d visual field loss in their teens and are generally registered as bli nd by their 30s. This ''bimodal expressivity'' contrasts with the vari able-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previo usly assumed to be recessive, might result from mutations at this locu s.