Mutational screening of the RP2 and RPGR genes in Spanish families with X-linked retinitis pigmentosa

PURPOSE. The X-linked form of retinitis pigmentosa ( XLRP) is the most severe type because of its early onset and rapid progression. Five XLRP loci have been mapped, although only two genes, RPGR ( for RP3) and RP2, have been cloned. In this study, 30 unrelated XLRP Spanish families were screened to determine the molecular cause of the disease. METHODS. Haplotype analysis was performed, to determine whether the disease is linked to the RP3 or RP2 region. In those families in which the disease cosegregates with either locus, mutational screening was performed. The RP2 gene, the first 15 exons of RPGR at the cDNA level, and the open reading frame ( ORF) 14 and 15 exons were screened at the genomic DNA level. RESULTS. Haplotype analysis ruled out the implication in the disease of RP2 in six families and of RPGR in four families. Among the 30 unrelated XLRP families, there 4 mutations were identified in RP2 ( 13%), 3 of which are novel, and 16 mutations in RPGR ( 53.3%), 7 of which are novel. CONCLUSIONS. In this cohort of XLRP families, as has happened in previous studies, RP3 also seems to be the most prevalent form of XLRP, and, based on the results, the authors propose a four-step protocol for molecular diagnosis of XLRP families.