A NOVEL LOCUS (RP24) FOR X-LINKED RETINITIS-PIGMENTOSA MAPS TO XQ26-27

Two genetic loci, RP2 and RP3, for X-linked retinitis pigmentosa (XLRP ) have been localized to Xp11.3-11.23 and Xp21.1, respectively. RP3 ap pears to account for 70% of XLRP families; however, mutations in the R PGR gene (isolated from the RP3 region) are identified in only 20% of affected families. Close location of XLRP loci at Xp and a lack of una mbiguous clinical criteria do not permit assignment of genetic subtype in a majority of XLRP families; nonetheless, in some pedigrees, both RP2 and RP3 could be excluded as the causative locus. We report the ma pping of a novel locus, RP24, by haplotype and linkage analysis of a s ingle XLRP pedigree. The RP24 locus was identified at Xq26-27 by genot yping 52 microsatellite markers spanning the entire X chromosome. A ma ximum LOD score of 4.21 was obtained with DXS8106. Haplotype analysis assigned RP24 within a 23-cM region between the DXS8094 (proximal) and DXS8043 (distal) markers. Other chromosomal regions and known XLRP lo ci were excluded by obligate recombination events between markers in t hose regions and the disease locus. Hemizygotes from the RP24 family h ave early onset of rod photoreceptor dysfunction; cone receptor functi on is normal at first, but there is progressive loss. Patients at adva nced stages show little or no detectable rod or cone function and have clinical hallmarks of typical RP. Mapping of the RP24 locus expands o ur understanding of the genetic heterogeneity in XLRP and will assist in development of better tools for diagnosis.