Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1998 Nov;63(5):1439–1447. doi: 10.1086/302121

A novel locus (RP24) for X-linked retinitis pigmentosa maps to Xq26-27.

L Gieser 1, R Fujita 1, H H Göring 1, J Ott 1, D R Hoffman 1, A V Cideciyan 1, D G Birch 1, S G Jacobson 1, A Swaroop 1
PMCID: PMC1377555  PMID: 9792872

Abstract

Two genetic loci, RP2 and RP3, for X-linked retinitis pigmentosa (XLRP) have been localized to Xp11.3-11.23 and Xp21.1, respectively. RP3 appears to account for 70% of XLRP families; however, mutations in the RPGR gene (isolated from the RP3 region) are identified in only 20% of affected families. Close location of XLRP loci at Xp and a lack of unambiguous clinical criteria do not permit assignment of genetic subtype in a majority of XLRP families; nonetheless, in some pedigrees, both RP2 and RP3 could be excluded as the causative locus. We report the mapping of a novel locus, RP24, by haplotype and linkage analysis of a single XLRP pedigree. The RP24 locus was identified at Xq26-27 by genotyping 52 microsatellite markers spanning the entire X chromosome. A maximum LOD score of 4.21 was obtained with DXS8106. Haplotype analysis assigned RP24 within a 23-cM region between the DXS8094 (proximal) and DXS8043 (distal) markers. Other chromosomal regions and known XLRP loci were excluded by obligate recombination events between markers in those regions and the disease locus. Hemizygotes from the RP24 family have early onset of rod photoreceptor dysfunction; cone receptor function is normal at first, but there is progressive loss. Patients at advanced stages show little or no detectable rod or cone function and have clinical hallmarks of typical RP. Mapping of the RP24 locus expands our understanding of the genetic heterogeneity in XLRP and will assist in development of better tools for diagnosis.

Full Text

The Full Text of this article is available as a PDF (546.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aldred M. A., Teague P. W., Jay M., Bundey S., Redmond R. M., Jay B., Bird A. C., Bhattacharya S. S., Wright A. F. Retinitis pigmentosa families showing apparent X linked inheritance but unlinked to the RP2 or RP3 loci. J Med Genet. 1994 Nov;31(11):848–852. doi: 10.1136/jmg.31.11.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Becker A., Geiger D., Schäffer A. A. Automatic selection of loop breakers for genetic linkage analysis. Hum Hered. 1998 Jan-Feb;48(1):49–60. doi: 10.1159/000022781. [DOI] [PubMed] [Google Scholar]
  3. Bergen A. A., Pinckers A. J. Localization of a novel X-linked progressive cone dystrophy gene to Xq27: evidence for genetic heterogeneity. Am J Hum Genet. 1997 Jun;60(6):1468–1473. doi: 10.1086/515458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berson E. L., Rosen J. B., Simonoff E. A. Electroretinographic testing as an aid in detection of carriers of X-chromosome-linked retinitis pigmentosa. Am J Ophthalmol. 1979 Apr;87(4):460–468. doi: 10.1016/0002-9394(79)90231-9. [DOI] [PubMed] [Google Scholar]
  5. Bhattacharya S. S., Wright A. F., Clayton J. F., Price W. H., Phillips C. I., McKeown C. M., Jay M., Bird A. C., Pearson P. L., Southern E. M. Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28. Nature. 1984 May 17;309(5965):253–255. doi: 10.1038/309253a0. [DOI] [PubMed] [Google Scholar]
  6. Birch D. G., Fish G. E. Rod ERGs in retinitis pigmentosa and cone-rod degeneration. Invest Ophthalmol Vis Sci. 1987 Jan;28(1):140–150. [PubMed] [Google Scholar]
  7. Buraczynska M., Wu W., Fujita R., Buraczynska K., Phelps E., Andréasson S., Bennett J., Birch D. G., Fishman G. A., Hoffman D. R. Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa. Am J Hum Genet. 1997 Dec;61(6):1287–1292. doi: 10.1086/301646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen Y. T., Rettig W. J., Yenamandra A. K., Kozak C. A., Chaganti R. S., Posner J. B., Old L. J. Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3077–3081. doi: 10.1073/pnas.87.8.3077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cideciyan A. V., Hood D. C., Huang Y., Banin E., Li Z. Y., Stone E. M., Milam A. H., Jacobson S. G. Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7103–7108. doi: 10.1073/pnas.95.12.7103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cideciyan A. V., Jacobson S. G. Negative electroretinograms in retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1993 Nov;34(12):3253–3263. [PubMed] [Google Scholar]
  11. Fishman G. A., Weinberg A. B., McMahon T. T. X-linked recessive retinitis pigmentosa. Clinical characteristics of carriers. Arch Ophthalmol. 1986 Sep;104(9):1329–1335. doi: 10.1001/archopht.1986.01050210083030. [DOI] [PubMed] [Google Scholar]
  12. Fujita R., Buraczynska M., Gieser L., Wu W., Forsythe P., Abrahamson M., Jacobson S. G., Sieving P. A., Andréasson S., Swaroop A. 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 two families. Am J Hum Genet. 1997 Sep;61(3):571–580. doi: 10.1086/515523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jacobson S. G., Buraczynska M., Milam A. H., Chen C., Järvaläinen M., Fujita R., Wu W., Huang Y., Cideciyan A. V., Swaroop A. Disease expression in X-linked retinitis pigmentosa caused by a putative null mutation in the RPGR gene. Invest Ophthalmol Vis Sci. 1997 Sep;38(10):1983–1997. [PubMed] [Google Scholar]
  14. Jacobson S. G., Yagasaki K., Feuer W. J., Román A. J. Interocular asymmetry of visual function in heterozygotes of X-linked retinitis pigmentosa. Exp Eye Res. 1989 May;48(5):679–691. doi: 10.1016/0014-4835(89)90009-2. [DOI] [PubMed] [Google Scholar]
  15. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Li Z. Y., Wong F., Chang J. H., Possin D. E., Hao Y., Petters R. M., Milam A. H. Rhodopsin transgenic pigs as a model for human retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1998 Apr;39(5):808–819. [PubMed] [Google Scholar]
  17. McGuire R. E., Sullivan L. S., Blanton S. H., Church M. W., Heckenlively J. R., Daiger S. P. X-linked dominant cone-rod degeneration: linkage mapping of a new locus for retinitis pigmentosa (RP 15) to Xp22.13-p22.11. Am J Hum Genet. 1995 Jul;57(1):87–94. [PMC free article] [PubMed] [Google Scholar]
  18. Meindl A., Dry K., Herrmann K., Manson F., Ciccodicola A., Edgar A., Carvalho M. R., Achatz H., Hellebrand H., Lennon A. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nat Genet. 1996 May;13(1):35–42. doi: 10.1038/ng0596-35. [DOI] [PubMed] [Google Scholar]
  19. Musarella M. A., Anson-Cartwright L., Leal S. M., Gilbert L. D., Worton R. G., Fishman G. A., Ott J. Multipoint linkage analysis and heterogeneity testing in 20 X-linked retinitis pigmentosa families. Genomics. 1990 Oct;8(2):286–296. doi: 10.1016/0888-7543(90)90284-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ott J., Bhattacharya S., Chen J. D., Denton M. J., Donald J., Dubay C., Farrar G. J., Fishman G. A., Frey D., Gal A. Localizing multiple X chromosome-linked retinitis pigmentosa loci using multilocus homogeneity tests. Proc Natl Acad Sci U S A. 1990 Jan;87(2):701–704. doi: 10.1073/pnas.87.2.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Roepman R., van Duijnhoven G., Rosenberg T., Pinckers A. J., Bleeker-Wagemakers L. M., Bergen A. A., Post J., Beck A., Reinhardt R., Ropers H. H. Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1. Hum Mol Genet. 1996 Jul;5(7):1035–1041. doi: 10.1093/hmg/5.7.1035. [DOI] [PubMed] [Google Scholar]
  22. Roof D. J., Adamian M., Hayes A. Rhodopsin accumulation at abnormal sites in retinas of mice with a human P23H rhodopsin transgene. Invest Ophthalmol Vis Sci. 1994 Nov;35(12):4049–4062. [PubMed] [Google Scholar]
  23. Schwahn U., Lenzner S., Dong J., Feil S., Hinzmann B., van Duijnhoven G., Kirschner R., Hemberger M., Bergen A. A., Rosenberg T. Positional cloning of the gene for X-linked retinitis pigmentosa 2. Nat Genet. 1998 Aug;19(4):327–332. doi: 10.1038/1214. [DOI] [PubMed] [Google Scholar]
  24. Teague P. W., Aldred M. A., Jay M., Dempster M., Harrison C., Carothers A. D., Hardwick L. J., Evans H. J., Strain L., Brock D. J. Heterogeneity analysis in 40 X-linked retinitis pigmentosa families. Am J Hum Genet. 1994 Jul;55(1):105–111. [PMC free article] [PubMed] [Google Scholar]
  25. Thiselton D. L., Hampson R. M., Nayudu M., Van Maldergem L., Wolf M. L., Saha B. K., Bhattacharya S. S., Hardcastle A. J. Mapping the RP2 locus for X-linked retinitis pigmentosa on proximal Xp: a genetically defined 5-cM critical region and exclusion of candidate genes by physical mapping. Genome Res. 1996 Nov;6(11):1093–1102. doi: 10.1101/gr.6.11.1093. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES