ANALYSIS OF 3 DELETION BREAKPOINTS IN XP21.1 AND THE FURTHER LOCALIZATION OF RP3

The gene responsible for X-Linked retinitis pigmentosa (xIRP) in Xp21. 1 (RP3) was initially localized by deletion analysis to within a 150- to 170-kb region between the CYBB locus and the proximal deletion junc tion (BBJ(PROX)) from a patient, BB, who suffered from Duchenne muscul ar dystrophy (DMD), McLeod syndrome, chronic granulomatous disease (CG D), and xIRP. This gene has recently been isolated and was found to be located outside and 400 kb proximal to the BB deletion. Further analy sis of BBJ(PROX) has identified the breakpoint junction sequence, show ing that it occurs within an Alu repetitive element on the proximal si de but with no significant homology to the distal sequence in dystroph in intron 30. Analysis of an overlapping deletion in patient NF, who s uffered from DMD, CGD, and McLeod syndrome, shows that this deletion i s within 4 kb but extends centromeric to BBJ(PROX), consistent with th e location of RP3 outside the BB deletion region. A sequence with stro ng homology to a THE-1 transposon-like element was identified 7-13 kb from the proximal BB and NF breakpoints. These elements have been impl icated in several highly unstable genomic regions. A third overlapping deletion, in a patient, SB, who suffered from CGD, McLeod syndrome, a nd xIRP, has here been shown to extend 380 kb proximal to the NF break point, consistent with the finding that RP3 Lies outside the BB deleti on. This deletion has now been shown to disrupt the RP3 (RPGR) gene. T he reason for the retinitis pigmentosa phenotype in patient BB remains unclear, but the most likely explanations include a long-range chromo somal position effect, a small secondary rearrangement, and the presen ce of a coincident autosomal form of retinitis pigmentosa. (C) 1996 Ac ademic Press, Inc.