Identification of novel RP2 mutations in a subset of X-linked Retinitis Pigmentosa families and prediction of new domains

X-Iinked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity wit h almost five dis, tinct loci on the X chromosome. So far, only two XLRP ge nes have been identified, RPGR (or RP3) and RP2, being mutated in approxima tely 70% and 10% of the XLRP patients. Clinically there is no clearly signi ficative difference between RP3 and RP2 phenotypes. In the attempt to asses s the degree of involvement of the RP2 gene, we performed a complete mutati on analysis in a cohort of patients and we identified five novel mutations in five different XLRP families. These mutations include three missense mut ations, a splice site mutation, and a single base insertion, which, because of frameshift, anticipates a stop codon. Four mutations fall in RP2 exon 2 and one in exon 3. Evidence that such mutations are different from the 21 RP2 mutations described thus far suggests that a high mutation rate occurs at the RP2 locus, and that most mutations arise independently, without a fo under effect. Our mutation analysis confirms the percentage of RP2 mutation s detected so far in populations of different ethnic origin. In addition to novel mutations, we report here that a deeper sequence analysis of the RP2 product predicts, in addition to cofactor C homology domain, further putat ive functional domains, and that some novel mutations identify RP2 amino ac id residues which are evolutionary conserved, hence possibly crucial to the RP2 function. Hum Mutat 18:109-119, 2001. (C) 2001 Wiley-Liss, Inc.