Possible Assignment of a Dominant Retinitis pigmentosa Gene to Chromosome

Abstract

A genetic linkage study, performed on a large family with autosomal dominant retinitis pigmentosa (RP), demonstrated that the RP gene may be linked to the Rh locus, known to be on the short arm of human chromosome 1. Linkage studies on RP along with other studies, can help to more accurately classify these disease entities. Localizing the RP gene locus has the potential for allowing the early diagnosis of individuals at risk.

Linkage analysis of human chromosome 4: exclusion of autosomal dominant retinitis pigmentosa (ADRP) and detection of new linkage groups

“…UCLA-RP0I. is part of a seven-generation family described by Spence et al (1977) and Field et al (1982). The pedigree is D aiger H um phries G iesenschlag S h arp M cW illiam F a rre r B radley K cnna M cC onnell Sparkes Spence Heckenlivcly H um phries I.…”

“…The Xlinkcd form has been mapped to Xpl 1 based on linkage to several DNA markers, with a second possible site at Xp21 (Bhattacharya etal., 1984;Friedrich el al" 1985;Nussbaumetal., 1985;Farrar et al, 1988;Musarella et al, 1988). No significant linkages for the autosomal forms of retinitis pigmentosa have been reported; how ever, there is suggestive evidence for linkage of at least one form of autosomal dominant retinitis pigmentosa (ADRP) to the Rh blood group on chromosome lp (Spence et al, 1977;Field et al, 1982;Daiger et al. 1987c) and for linkage of Usher syndrome, a recessive form of retinitis pigmentosa accompanied by congenital deafness, to GC protein on chromosome 4q (Daiger et al, 1987a;Pelias et al, 1989).…”

“…The pedigree in Fig. 2 differs from the pedigree in Field et al [1982] because of the addition of new members and because the order within sibships has been rearranged to reflect birth order.) There arc over 100 known, affected members in the extended UCLA-RP01 family.…”

“…An additional 47 in dividuals were included in the analysis as links between sampled individuals. Of the total of 156 individuals included in the analysis, classical genetic markers had been tested in 68 individuals as part of earlier studies (Spence el al., 1977;Field et al. 1982).…”

Genetic Factors Modifying Clinical Expression of Autosomal Dominant RP

“…Over 100 living, affected family members have been identified by pedigree reconstruction (Blanton et al, 1991). The family has been the subject of clinical and genetic studies for more that 30 years, including field studies in Kentucky and ophthalmic evaluations at the Jules Stein Eye Institute, UCLA Heckenlively et al, 1982;Lehmer et al, 1992). RP01 has classical type 2 adRP with late onset of night blindness, usually by the third decade of life, and slow progression.…”