In the May 1996 issue of Nature Genetics , a team led by Drs. The uphill struggle involved in the RP3 gene cloning was complicated by the genetic heterogeneity in XLRP and by the chromosomal deletion in a patient BB that misled the search. Suggestion of Another Locus at Xp21. Another locus RP15 mapped at Xp22. Attempts to define RP2 or RP3 using the onset of myopia, night blindness, or tapetal reflex remain inconclusive.
Genetic analysis provides the only means for distinguishing between the two major XLRP subtypes.
The clustering of loci at Xp also makes it difficult to genetically discriminate among the RP loci in XLRP families, especially between the two prevalent subtypes RP3 and RP2. This labor-intensive approach requires the genetic analysis of affected families with polymorphic markers to determine the chromosomal location of the disease locus. This study, however, is greatly facilitated by gross chromosomal rearrangements, which can provide a focus for molecular analysis by pointing to a specific genomic region. The XLRP locus RP3 was believed to be in the proximal portion of the BB deletion because of its coincidence with the critical region delineated by linkage analysis. We and others, therefore, have been searching for the transcribed sequences in this region surrounding the proximal breakpoint for several years.