Positional cloning of the gene for X-linked retinitis pigmentosa 2


X-linked retinitis pigmentosa (XLRP) results from mutations in at least two different loci, designated RP2 and RP3, located at Xp11.3 and Xp21.1, respectively. The RP3 gene was recently isolated by positional cloning, whereas the RP2 locus was mapped genetically to a 5-cM interval. We have screened this region for genomic rearrangements by the YAC representation hybridization (YRH) technique and detected a LINE1 (L1) insertion in one XLRP patient. The L1 retrotransposition occurred in an intron of a novel gene that consisted of five exons and encoded a polypeptide of 350 amino acids. Subsequently, nonsense, missense and frameshift mutations, as well as two small deletions, were identified in six additional patients. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of ß-tubulin folding. Our data provide evidence that mutations in this gene, designated RP2, are responsible for progressive retinal degeneration.

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Figure 1: Physical map of the RP2 linkage interval in Xp11.3-p11.23, between the markers DXS7 and OATL1.
Figure 2: Molecular characterization of the L1 insertion in patient 2967.
Figure 3: Northern-blot analysis of fetal human and adult mouse tissues.
Figure 4: Sequence analysis of RP2 and its exon-intron structure.
Figure 5: Mutation analysis in XLRP patients.


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The authors are very grateful to the patients and their families who contributed to this study. We would like to thank the Ressourcenzentrum im Deutschen Humangenomprojekt, the UK HGMP Resource Center (Hinxton) and the YAC Screening Center Leiden, The Netherlands, for providing us with genomic and cDNA libraries. We also wish to thank S. Freier and S.v.d. Velde-Visser for tissue culturing, C. Zeitz and M. Krause for technical assistance, M.R. Toliat for assistance during characterization of the cDNA and A.d. Hollander for making available total RNA from adult human retina. This work was supported in part by the Deutsche Forschungsgemeinschaft (SL, grant Be 1559/2-1) and the Foundation Fighting Blindness, USA (R.K.).

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Correspondence to Wolfgang Berger.

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Schwahn, U., Lenzner, S., Dong, J. et al. Positional cloning of the gene for X-linked retinitis pigmentosa 2. Nat Genet 19, 327–332 (1998). https://doi.org/10.1038/1214

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