Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease — a contiguous gene syndrome

Nature Genetics volume 8, pages 328–332 (1994)Cite this article

Abstract

Major genes which cause tuberous sclerosis (TSC) and autosomal dominant polycystic kidney disease (ADPKD), known as TSC2 and PKD1 respectively, lie immediately adjacent to each other on chomosome 16p. Renal cysts are often found in TSC, but a specific renal phenotype, distinguished by the severity and infantile presentation of the cystic changes, is seen in a small proportion of cases. We have identified large deletions disrupting TSC2 and PKD1 in each of six such cases studied. Analysis of the deletions indicates that they inactivate PKD1, in contrast to the mutations reported in ADPKD patients, where in each case abnormal transcripts have been detected.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gomez, M.R., Tuberous Sclerosis, 2nd edition (Raven Press, New York, 1988).

  2. Shepherd, C.W., Gomez, M.R. & Lie, J.T. Causes of death in patients with tuberous sclerosis. Mayo Clin. Proc. 66, 792–796 (1991).

    Article  CAS  Google Scholar 

  3. Green, A.J., Smith, M. & Yates, J.R.W. Loss of heterozygosity on chromosome 16p in hamartomas from tuberous sclerosis patients. Nature Genet. 6, 193–196 (1994).

    Article  CAS  Google Scholar 

  4. Green, A.J. & Yates, J.R.W. The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor. Hum. molec. Genet. 3, 1833–1837 (1994).

    Article  CAS  Google Scholar 

  5. Stillwell, T.J., Gomez, M.R. & Kelalis, P.P. Renal lesions in tuberous sclerosis. J. Urol. 138, 477–481 (1987).

    Article  CAS  Google Scholar 

  6. van Baal, J.G., Fleury, P. & Brummelkamp, H. Tuberous sclerosis and the relation with renal angiomyolipoma. A genetic study on the clinical aspects. Clin. Genet. 35, 167–173 (1989).

    Article  CAS  Google Scholar 

  7. Zimmerhackl, L.B., Rehm, M., Kaufmehl, K. & Brandis, M. Renal involvement in tuberous sclerosis complex: a retrospective survey. Pediat Nephrol. (in the press).

  8. Cree, J.E. Tuberous sclerosis with polycystic kidneys. Proc. R. Soc. Med. 62, 327 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wenzl, J.E., Largos, J.C. & Albers, D.D. Tuberous sclerosis presenting as polycystic kidneys in an infant. J. Pediatr. 77, 673–676 (1970).

    Article  CAS  Google Scholar 

  10. O'Callaghan, T.J., Edwards, J.A., Tobin, M. & Mookerjee, B.K. Tuberous sclerosis with striking renal involvement in a family. Arch. intern. Med. 135, 1082–1087 (1975).

    Article  CAS  Google Scholar 

  11. Stapleton, F.B., Johnson, D., Kaplan, G.W. & Griswold, W. The cystic renal lesion in tuberous sclerosis. J. Pediatr. 97, 574–579 (1980).

    Article  CAS  Google Scholar 

  12. Webb, D.W., Super, M., Normand, C.S. & Osborne, J.P. Tuberous sclerosis and polycystic kidney disease. Brit. med. J. 306, 1258–1259 (1993).

    Article  CAS  Google Scholar 

  13. The European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterisation of the tuberous sclerosis gene on chromosome 16. Cell 75, 1305–1315 (1993).

  14. The European Polycystic kidney disease 1 gene encodes a 14kb transcript and lies within a duplicated region on chromosome 16. Cell 77, 881–894 (1994).

    Article  Google Scholar 

  15. Nellist, M., Brook-Carter, P.T., Connor, J.M., Kwiatkowski, D.J., Johnson, P. & Sampson, J. Identification of markers flanking the tuberous sclerosis locus on chromosome 9 (TSC1). J. med. Genet. 30, 224–227 (1993).

    Article  CAS  Google Scholar 

  16. Cole, B.R., Conley, S.B. & Stapleton, F.B. Polycystic kidney disease in the first year of life. J. Pediatr. 111, 693–699 (1987).

    Article  CAS  Google Scholar 

  17. Schmickel, R.D. Contiguous gene syndromes: a component of recognizable syndromes. J. Pediatr. 109, 231–241 (1986).

    Article  CAS  Google Scholar 

  18. Fink, G.M. et at. Characteristics of very early onset autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 3, 1863–1870 (1993).

    Google Scholar 

  19. Bernstein, J. & Robbins, T.O. Renal involvement in tuberous sclerosis. Ann. N. Y. Acad. Sci. 615, 36–49 (1991).

    Article  CAS  Google Scholar 

  20. Zerres, K., Rudnik-Schönebom, S. & Deget, F. Childhood onset autosomal dominant polycystic kidney disease in sibs: clinical picture and recurrence risk. J. med. Genet. 30, 583–588 (1993).

    Article  CAS  Google Scholar 

  21. Fink, G.M., Johnson, A.M. & Gabow, P.A. Is there evidence for anticipation in autosomal dominant polycystic kidney disease? Kidney Int. 40, 1153–1162 (1994).

    Google Scholar 

  22. Mandel, J.-L. Questions of expansion. Nature Genet. 4, 8–9 (1993).

    Article  CAS  Google Scholar 

  23. Hermann, B.G., Barlow, D.P. & Lehrach, H. A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion. Cell 48, 813–825 (1987).

    Article  Google Scholar 

  24. Sambrook, J., Fritsch, E.F. & Maniatis, T. Molecular cloning: a laboratory manual. 2nd edn (Cold Spring Harbor, Laboratory Press, New York, 1989).

    Google Scholar 

  25. Peral, B. et al. Evidence of linkage disequilibrium in the Spanish polycystic kidney disease 1 population. Am. J. hum Genet. 54, 899–908 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Pinkel, D. et al. Fluorescence in situ hybridization with human chromosome specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc. Natn. Acad. Sci. U.S.A 85, 9138–9142 (1988).

    Article  CAS  Google Scholar 

  27. Lichter, P. et al. High resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247, 64–68 (1990).

    Article  CAS  Google Scholar 

  28. Frohman, M.A., Dush, M.K. & Martin, G.R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonudeotide primer. Biochemistry 85, 8998–9002 (1988).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, CF4 4XN, UK

    Phillip T. Brook-Carter, Peter Thompson, Magitha M. Maheshwar, Mark Nellist & Julian R. Sampson

  2. Medical Research Council Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Belén Peral, Christopher J. Ward, Jim Hughes, Vicki Gamble & Peter C. Harris

Authors
  1. Phillip T. Brook-Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Belén Peral
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher J. Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jim Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Magitha M. Maheshwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mark Nellist
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vicki Gamble
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peter C. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Julian R. Sampson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brook-Carter, P., Peral, B., Ward, C. et al. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease — a contiguous gene syndrome. Nat Genet 8, 328–332 (1994). https://doi.org/10.1038/ng1294-328

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1294-328

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing