ANALYSIS OF THE RPGR GENE IN 11 PEDIGREES WITH THE RETINITIS-PIGMENTOSA TYPE-3 GENOTYPE - PAUCITY OF MUTATIONS IN THE CODING REGION BUT SPLICE DEFECTS IN 2 FAMILIES

X-linked retinitis pigmentosa (XLRP) is a severe form of inherited pro gressive retinal degeneration. The RP3 (retinitis pigmentosa type (3) under bar locus at Xp21.1 is believed to account for the disease in th e majority of XLRP families. Linkage analysis and identification of pa tients with chromosomal deletion have refined the location of the RP3 locus and recently have led to the cloning of the RPGR (retinitis pigm entosa GTPase regulator) gene, which has been shown to be mutated in 1 0%-15% of XLRP patients. In order to systematically characterize the R PGR mutations, we identified 11 retinitis pigmentosa type III (RP3) fa milies by haplotype analysis. Sequence analysis of the PCR-amplified g enomic DNA from patients representing these RP3 families did not revea l any causative mutation in RPGR exons 2-19, spanning >98% of the codi ng region. In patients from two families, we identified transition mut ations in the intron region near splice sites (IVS10+3 and IVS13-8). R NA analysis showed that both splice-site mutations resulted in the gen eration of aberrant RPGR transcripts. Our results support the hypothes is that mutations in the reported RPGR gene are not a common defect in the RP3 subtype of XLRP and that a majority of causative mutations ma y reside either in as yet unidentified RPGR exons or in another nearby gene at Xp21.1.