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. 1990 Oct;47(4):622–628.

Deletions in patients with classical choroideremia vary in size from 45 kb to several megabases

Frans P M Cremers, Eeva-Marja Sankila, Frank Brunsmann, Marcelle Jay, Barrie Jay, Alan Wright, Alfred J L G Pinckers, Marianne Schwartz, Dorien J R van de Pol, Bé Wieringa, Albert de la Chapelle, Ivar H Pawlowitzki, Hans-Hilger Ropers
PMCID: PMC1683797  PMID: 2220804

Abstract

Making use of the p1bD5 probe (DXS165), we have isolated several markers from the choroideremia locus by chromosomal jumping, preparative field-inversion gel electrophoresis, and cloning of a deletion junction fragment. With these clones we were able to identify and characterize eight deletions in 69 choroideremia patients investigated. The deletions are heterogeneous, in both size and location. The smallest deletion (patient LGL1134) comprises approximately 45 kb of DNA, whereas the largest ones (patients 25.6 and LGL2905) span a DNA segment of at least 5 megabases, which is comparable in size to the smallest deletion detected in a TCD patient (patient XL45) showing a complex phenotype. The TCD deletions encompass variable parts of a 150–200-kb DNA segment that is flanked by p1bD5 (DXS165) at the centromeric side and by pZ11 at the telomeric side. The deletions in patients 33.1, LGL1101, and LGL1134 do not span a translocation breakpoint which was previously mapped on the X chromosome of a female with TCD. The clones isolated from the TCD locus are valuable diagnostic markers for deletion analysis of patients or carrier females. In addition, they should be useful for the isolation of expressed sequences that are part of the TCD gene.

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Selected References

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

  1. Aldridge J., Kunkel L., Bruns G., Tantravahi U., Lalande M., Brewster T., Moreau E., Wilson M., Bromley W., Roderick T. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PMC free article] [PubMed] [Google Scholar]
  2. Chu G., Vollrath D., Davis R. W. Separation of large DNA molecules by contour-clamped homogeneous electric fields. Science. 1986 Dec 19;234(4783):1582–1585. doi: 10.1126/science.3538420. [DOI] [PubMed] [Google Scholar]
  3. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cremers F. P., Brunsmann F., van de Pol T. J., Pawlowitzki I. H., Paulsen K., Wieringa B., Ropers H. H. Deletion of the DXS165 locus in patients with classical choroideremia. Clin Genet. 1987 Dec;32(6):421–423. doi: 10.1111/j.1399-0004.1987.tb03166.x. [DOI] [PubMed] [Google Scholar]
  5. Cremers F. P., Pfeiffer R. A., van de Pol T. J., Hofker M. H., Kruse T. A., Wieringa B., Ropers H. H. An interstitial duplication of the X chromosome in a male allows physical fine mapping of probes from the Xq13-q22 region. Hum Genet. 1987 Sep;77(1):23–27. doi: 10.1007/BF00284707. [DOI] [PubMed] [Google Scholar]
  6. Cremers F. P., van de Pol D. J., Diergaarde P. J., Wieringa B., Nussbaum R. L., Schwartz M., Ropers H. H. Physical fine mapping of the choroideremia locus using Xq21 deletions associated with complex syndromes. Genomics. 1989 Jan;4(1):41–46. doi: 10.1016/0888-7543(89)90312-1. [DOI] [PubMed] [Google Scholar]
  7. Cremers F. P., van de Pol D. J., Wieringa B., Collins F. S., Sankila E. M., Siu V. M., Flintoff W. F., Brunsmann F., Blonden L. A., Ropers H. H. Chromosomal jumping from the DXS165 locus allows molecular characterization of four microdeletions and a de novo chromosome X/13 translocation associated with choroideremia. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7510–7514. doi: 10.1073/pnas.86.19.7510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cremers F. P., van de Pol T. J., Wieringa B., Hofker M. H., Pearson P. L., Pfeiffer R. A., Mikkelsen M., Tabor A., Ropers H. H. Molecular analysis of male-viable deletions and duplications allows ordering of 52 DNA probes on proximal Xq. Am J Hum Genet. 1988 Oct;43(4):452–461. [PMC free article] [PubMed] [Google Scholar]
  9. Curry C. J., Magenis R. E., Brown M., Lanman J. T., Jr, Tsai J., O'Lague P., Goodfellow P., Mohandas T., Bergner E. A., Shapiro L. J. Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome. N Engl J Med. 1984 Oct 18;311(16):1010–1015. doi: 10.1056/NEJM198410183111603. [DOI] [PubMed] [Google Scholar]
  10. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  11. Francke U., Ochs H. D., de Martinville B., Giacalone J., Lindgren V., Distèche C., Pagon R. A., Hofker M. H., van Ommen G. J., Pearson P. L. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. Am J Hum Genet. 1985 Mar;37(2):250–267. [PMC free article] [PubMed] [Google Scholar]
  12. Goodfellow P. N., Davies K. E., Ropers H. H. Report of the Committee on the Genetic Constitution of the X and Y Chromosomes. Cytogenet Cell Genet. 1985;40(1-4):296–352. doi: 10.1159/000132178. [DOI] [PubMed] [Google Scholar]
  13. Hodgson S. V., Robertson M. E., Fear C. N., Goodship J., Malcolm S., Jay B., Bobrow M., Pembrey M. E. Prenatal diagnosis of X-linked choroideremia with mental retardation, associated with a cytologically detectable X-chromosome deletion. Hum Genet. 1987 Mar;75(3):286–290. doi: 10.1007/BF00281076. [DOI] [PubMed] [Google Scholar]
  14. Jay M., Wright A. F., Clayton J. F., Deans M., Dempster M., Bhattacharya S. S., Jay B. A genetic linkage study of choroideremia. Ophthalmic Paediatr Genet. 1986 Dec;7(3):201–204. doi: 10.3109/13816818609004139. [DOI] [PubMed] [Google Scholar]
  15. Kärnä J. Choroideremia. A clinical and genetic study of 84 Finnish patients and 126 female carriers. Acta Ophthalmol Suppl. 1986;176:1–68. [PubMed] [Google Scholar]
  16. Lesko J. G., Lewis R. A., Nussbaum R. L. Multipoint linkage analysis of loci in the proximal long arm of the human X chromosome: application to mapping the choroideremia locus. Am J Hum Genet. 1987 Apr;40(4):303–311. [PMC free article] [PubMed] [Google Scholar]
  17. Lewis R. A., Nussbaum R. L., Ferrell R. Mapping X-linked ophthalmic diseases. Provisional assignment of the locus for choroideremia to Xq13-q24. Ophthalmology. 1985 Jun;92(6):800–806. doi: 10.1016/s0161-6420(85)33956-8. [DOI] [PubMed] [Google Scholar]
  18. Litt M., White R. L. A highly polymorphic locus in human DNA revealed by cosmid-derived probes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6206–6210. doi: 10.1073/pnas.82.18.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MacDonald I. M., Sandre R. M., Wong P., Hunter A. G., Tenniswood M. P. Linkage relationships of X-linked choroideremia to DXYS1 and DXS3. Hum Genet. 1987 Nov;77(3):233–235. doi: 10.1007/BF00284475. [DOI] [PubMed] [Google Scholar]
  20. Merry D. E., Lesko J. G., Siu V., Flintoff W. F., Collins F., Lewis R. A., Nussbaum R. L. DXS165 detects a translocation breakpoint in a woman with choroideremia and a de novo X; 13 translocation. Genomics. 1990 Apr;6(4):609–615. doi: 10.1016/0888-7543(90)90494-f. [DOI] [PubMed] [Google Scholar]
  21. Merry D. E., Lesko J. G., Sosnoski D. M., Lewis R. A., Lubinsky M., Trask B., van den Engh G., Collins F. S., Nussbaum R. L. Choroideremia and deafness with stapes fixation: a contiguous gene deletion syndrome in Xq21. Am J Hum Genet. 1989 Oct;45(4):530–540. [PMC free article] [PubMed] [Google Scholar]
  22. Nussbaum R. L., Lesko J. G., Lewis R. A., Ledbetter S. A., Ledbetter D. H. Isolation of anonymous DNA sequences from within a submicroscopic X chromosomal deletion in a patient with choroideremia, deafness, and mental retardation. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6521–6525. doi: 10.1073/pnas.84.18.6521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nussbaum R. L., Lewis R. A., Lesko J. G., Ferrell R. Choroideremia is linked to the restriction fragment length polymorphism DXYS1 at XQ13-21. Am J Hum Genet. 1985 May;37(3):473–481. [PMC free article] [PubMed] [Google Scholar]
  24. Rosenberg T., Schwartz M., Niebuhr E., Yang H. M., Sardemann H., Andersen O., Lundsteen C. Choroideremia in interstitial deletion of the X chromosome. Ophthalmic Paediatr Genet. 1986 Dec;7(3):205–210. doi: 10.3109/13816818609004140. [DOI] [PubMed] [Google Scholar]
  25. SORSBY A., FRANCESCHETTI A., JOSEPH R., DAVEY J. B. Choroideremia; clinical and genetic aspects. Br J Ophthalmol. 1952 Oct;36(10):547–581. doi: 10.1136/bjo.36.10.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saito F., Goto J., Kakinuma H., Nakamura F., Murayama S., Nakano I., Tonomura A. Inherited Xp21 deletion in a boy with complex glycerol kinase deficiency syndrome. Clin Genet. 1986 Jan;29(1):92–93. doi: 10.1111/j.1399-0004.1986.tb00777.x. [DOI] [PubMed] [Google Scholar]
  27. Sankila E. M., Bruns G. A., Schwartz M., Nikoskelainen E., Niebuhr E., Hodgson S. V., Wright A. F., de la Chapelle A. DXS26 (HU16) is located in Xq21.1. Hum Genet. 1990 Jun;85(1):117–120. doi: 10.1007/BF00276335. [DOI] [PubMed] [Google Scholar]
  28. Sankila E. M., Lehner T., Eriksson A. W., Forsius H., Kärnä J., Page D., Ott J., de la Chapelle A. Haplotype and multipoint linkage analysis in Finnish choroideremia families. Hum Genet. 1989 Dec;84(1):66–70. doi: 10.1007/BF00210674. [DOI] [PubMed] [Google Scholar]
  29. Sankila E. M., de la Chapelle A., Kärnä J., Forsius H., Frants R., Eriksson A. Choroideremia: close linkage to DXYS1 and DXYS12 demonstrated by segregation analysis and historical-genealogical evidence. Clin Genet. 1987 May;31(5):315–322. doi: 10.1111/j.1399-0004.1987.tb02815.x. [DOI] [PubMed] [Google Scholar]
  30. Schwartz M., Rosenberg T., Niebuhr E., Lundsteen C., Sardemann H., Andersen O., Yang H. M., Lamm L. U. Choroideremia: further evidence for assignment of the locus to Xq13-Xq21. Hum Genet. 1986 Dec;74(4):449–452. doi: 10.1007/BF00280505. [DOI] [PubMed] [Google Scholar]
  31. Schwartz M., Yang H. M., Niebuhr E., Rosenberg T., Page D. C. Regional localization of polymorphic DNA loci on the proximal long arm of the X chromosome using deletions associated with choroideremia. Hum Genet. 1988 Feb;78(2):156–160. doi: 10.1007/BF00278188. [DOI] [PubMed] [Google Scholar]
  32. Siu V. M., Gonder J. R., Jung J. H., Sergovich F. R., Flintoff W. F. Choroideremia associated with an X-autosomal translocation. Hum Genet. 1990 Apr;84(5):459–464. doi: 10.1007/BF00195820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wieringa B., Hustinx T., Scheres J., Renier W., ter Haar B. Complex glycerol kinase deficiency syndrome explained as X-chromosomal deletion. Clin Genet. 1985 May;27(5):522–523. doi: 10.1111/j.1399-0004.1985.tb00244.x. [DOI] [PubMed] [Google Scholar]
  34. van de Pol T. J., Cremers F. P., Brohet R. M., Wieringa B., Ropers H. H. Derivation of clones from the choroideremia locus by preparative field inversion gel electrophoresis. Nucleic Acids Res. 1990 Feb 25;18(4):725–731. doi: 10.1093/nar/18.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

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