Abstract
CHOROIDERAEMIA (tapetochoroidal dystrophy, TCD), a common form of X-linked blindness1, is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina2,3. Previous studies have assigned the TCD gene to a small segment of the Xq21 band4–6. By making use of reverse genetics strategies we have isolated eight overlapping complementary DNA clones from the same chromosomal region. The corresponding gene is expressed in retina, choroid and retinal pigment epithelium. The cDNAs encompass an open reading frame of 948 base pairs that is structurally altered in eight TCD patients with deletions, and in a female patient with a balanced translocation involving Xq21. These findings provide strong evidence that we have cloned the gene underlying choroideraemia. Elucidation of its function should provide new insights into the molecular mechanisms responsible for this disorder and other hereditary retinopathies.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Heckenlively, J. R. Retinitis pigmentosa (Lippincott, Philadelphia, 1988).
Goedbloed, J. Ophthalmologica 104, 308–315 (1942).
Waardenburg, P. J. Acta ophthalmol. 20, 235–274 (1942).
Cremers, F. P. M. et al. Clin. Genet. 32, 421–423 (1987).
Cremers, F. P. M. et al. Proc. natn. Acad. Sci. U.S.A. 86, 7510–7514 (1989).
Cremers, F. P. M. et al. Am. J. hum. Genet. (in the press).
Cremers, F. P. M. et al. Genomics 4, 41–46 (1989).
Merry, D. E. et al. Am. J. hum. Genet. 45, 530–540 (1989).
Cremers, F. P. M. et al. Hum. Genet. (in the press).
van de Pol, T. J. R., Cremers, F. P. M., Brohet, R. M., Wieringa, B. & Ropers, H.-H. Nucleic Acids Res. 18, 725–731 (1990).
Merry, D. E. et al. Genomics 6, 609–615 (1990).
Nathans, J., Thomas, D. & Hogness, D. S. Science 232, 193–202 (1986).
Padgett, R. A., Grabowski, P. J., Konarska, M. M., Seiler, S. & Sharp, P. A. A. Rev. Biochem. 55, 1119–1150 (1986).
Kozak, M. J. molec. Biol. 196, 947–950 (1987).
Siu, V. M., Gonder, J. R., Jung, I. H., Sergovich, F. R. & Flintoff, W. F. Hum. Genet. 84, 459–464 (1990).
Vaessen, R. T. M. J., Houweling, A., Israel, A., Kourilsky, P. & van der Eb, A. J. EMBO J. 5, 335–341 (1986).
Rogers, S., Wells, R. & Rechsteiner, M. Science 234, 364–368 (1986).
Rechsteiner, M., Rogers, S. & Rote, K. Trends Biochem. Sci. 12, 390–394 (1987).
Dryja, T. P. et al. Nature 343, 364–366 (1990).
Travis, G. H., Brennan, M. B., Danielson, P. E., Kozak, C. A. & Sutcliffe, J. G. Nature 338, 70–73 (1989).
Bowes, C., Danciger, M., Kozak, C. A. & Farber, D. B. Proc. natn. Acad. Sci. U.S.A. 86, 9722–9726 (1989).
Valle, D. & Simell, O. in The Metabolic Basis of Inherited Disease (eds. Stanbury, J. B., Wijngaarden, J. B., Fredrickson, D. S., Goldstein, J. L. & Brown, M. S.) 382–401 (McGraw-Hill, New York, 1983).
Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1989).
Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 137, 266–267 (1984).
Hattori, M. & Sakaki, Y. Analyt. Biochem. 152, 232–238 (1986).
Weaver, R. F. & Weissman, C. Nucleic Acids Res. 7, 1175–1193 (1979).
Dodemont, H. J. et al. EMBO J. 1, 167–171 (1982).
Auffray, C. & Rougeon, F. Eur. J. Biochem. 107, 303–314 (1980).
LeMeur, M. et al. Cell 23, 561–571 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cremers, F., van de Pol, D., van Kerkhoff, L. et al. Cloning of a gene that is rearranged in patients with choroideraemia. Nature 347, 674–677 (1990). https://doi.org/10.1038/347674a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/347674a0
This article is cited by
-
Molecular Therapy for Choroideremia: Pre-clinical and Clinical Progress to Date
Molecular Diagnosis & Therapy (2021)
-
Whole-exome sequencing identified a novel mutation in CHM of a Chinese family
Journal of Genetics (2021)
-
Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses
BMC Ophthalmology (2020)
-
Scleral pits represent degeneration around the posterior ciliary arteries and are signs of disease severity in choroideremia
Eye (2020)
-
Genetic defects of CHM and visual acuity outcome in 24 choroideremia patients from 16 Japanese families
Scientific Reports (2020)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
