[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
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:

Congenital adrenal hyperplasia due to point mutations in the type II 3β–hydroxysteroid dehydrogenase gene

Nature Genetics volume 1, pages 239–245 (1992)Cite this article

Abstract

Classical 3β–hydroxysteroid dehydrogenase /Δ5–Δ4–isomerase (3β–HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia characterized by a severe impairment of steroid biosynthesis in both the adrenals and the gonads. We describe the nucleotide sequence of the two highly homologous genes encoding 3β–HSD isoenzymes in three classic 3β–HSD deficient patients belonging to two apparently unrelated pedigrees. No mutation was detected in the type I 3β–HSD gene, which is mainly expressed in the placenta and peripheral tissues. Both nonsense and frameshift mutations, however, were found in the type II 3β–HSD gene, which is the predominant 3β–HSD gene expressed in the adrenals and gonads, thus providing the first elucidation of the molecular basis of this disorder.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • 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. New, M., White, P., Pang, S., Dupont, B. & Speiser, P.W. . in The Metabolic Basis of Inherited Diseases 6th edn (eds Scriver, C.R. et al.) 1881–1917 (McGraw-Hill Inc., New York, 1989).

    Google Scholar 

  2. Morel, Y. & Miller, W.L. Adv. hum. Genet. 20, 1–68 (1991).

    CAS  PubMed  Google Scholar 

  3. Zachmann, M., Tassinari, D. & Prader, A. J. clin. Endocrinol. Metab. 56, 222–229 (1983).

    Article  CAS  Google Scholar 

  4. White, P.C. et al. J. clin. Invest. 87, 1664–1667 (1991).

    Article  CAS  Google Scholar 

  5. Yanase, T., Simpson, E.R. & Waterman, M.R. Endocr. Rev. 12, 91–108 (1991).

    Article  CAS  Google Scholar 

  6. Bongiovanni, A.M. Fertil. Steril. 35, 599 (1981).

    Article  CAS  Google Scholar 

  7. Luu-The, V. et al. Molec. Endocrinol. 3, 1310–1312 (1989).

    Article  CAS  Google Scholar 

  8. Lachance, Y. et al. J. biol. Chem. 265, 20469–20475 (1990).

    CAS  PubMed  Google Scholar 

  9. Rhéaume, E. et al. Molec. Endocrinol. 5, 1147–1157 (1991).

    Article  Google Scholar 

  10. Lachance, Y. et al. DNA cell. Biol. 10, 701–711 (1991).

    Article  CAS  Google Scholar 

  11. Bongiovanni, A.M. & Kellenbenz, G. J. clin. Invest 41, 2086–2092 (1962).

    Article  CAS  Google Scholar 

  12. Parks, G.A., Bermudez, J.A., Anast, C.S., Bongiovanni, A.M. & New, M.I. J. clin. Endocrinol. 33, 269–278 (1971).

    Article  Google Scholar 

  13. Schneider, G., Genel, M., Bongiovanni, A.M., Goldman, A.S. & Rosenfield, R.L. J. clin. Invest. 55, 681–690 (1975).

    Article  CAS  Google Scholar 

  14. Zachmann, M., Völlmin, A., Mürset, G., Curtius, H.-C.H. & Prader, A. J. clin. Endocr. 30, 719–726 (1970).

    Article  CAS  Google Scholar 

  15. Zachmann, M., Forest, M.G. & de Peretti, E. Horm. Res. 11, 292–302 (1979).

    Article  CAS  Google Scholar 

  16. Cara, J.F., Moshang, T., Bongiovanni, A.M., Marx, B.S. New Engl. J. Med. 313, 618–621 (1985).

    Article  CAS  Google Scholar 

  17. . de Peretti, E. & Forest, M.G. Hormone Res. 16, 10–22 (1982).

    Article  CAS  Google Scholar 

  18. de Peretti, E., Forest, M.G., Feit, J.P. & David, M. in Adrenal Androgens. (eds Genazzani, A.R., Thijssen, J.H.H., & Siiteri,P.K.) 141–145 (Raven press, New York 1980).

    Google Scholar 

  19. Pang, S. et al. J. clin. Endocrinol. Metab. 56, 808–818 (1983).

    Article  CAS  Google Scholar 

  20. Gendrel, D., Chaussain, J.L., Roger, M. & Job, J.C. Arch. Franç. Pédiat. 36, 647–655 (1975).

    Google Scholar 

  21. Rosenfield, R.L. et al. J. clin. Endocrinol. Metab. 51, 345–353 (1980).

    Article  CAS  Google Scholar 

  22. Mendoca, B.B. et al. J. Steroid Biochem. 28, 669–675 (1987).

    Article  Google Scholar 

  23. Bérubé, D., Luu-The, V., Lachance, Y., Gagné, R. & Labrie, F. Cytogen. Cell. Genet. 52, 199–200 (1989).

    Article  Google Scholar 

  24. Zachmann, M., Kempken, B., Anner, I. & Pezzoli, V. Ped. Res. 24, 543 (1988).

    Article  Google Scholar 

  25. Rhéaume, E., Leblanc, J.F., Lachance, Y., Labrie, F. & Simard, J., Hum. Genet. 87, 753–754 (1991).

    Article  Google Scholar 

  26. Rhéaume, E., Sirois, I., Labrie, F. & Simard, J. Nucl. Acid Res. 19, 6060 (1991).

    Article  Google Scholar 

  27. Rosenfield, R.L., de Niepomniszsze, A.B., Kenny, F.M. & Genel, M. J. clin. endo. Metab. 39, 370–374 (1974).

    Article  CAS  Google Scholar 

  28. Goldman, A.S., Yakovac, W.C. & Bongiovanni, A.M. J. clin. endo. Metab. 26, 14–22 (1966).

    Article  CAS  Google Scholar 

  29. Milewich, L. et al. J. clin. endo. Metab. 73, 1134–1140 (1991).

    Article  CAS  Google Scholar 

  30. Dupont, E., Luu-The, V., Labrie, F. & Pelletier, G. J. Androl. 12, 161–164 (1990).

    Google Scholar 

  31. Grumbach, M.M. & Conte, F.A. in Williams Textbook of Endocinology, 8th edn (eds Wilson.J.D. & Foster, D.W.) 853–951 (Saunders, Montréal, 1992).

    Google Scholar 

  32. Dupont, E., Labrie, F., Luu-The, V. & Pelletier, G. J. clin. Endo. Metab. 74, 994–998 (1992).

    CAS  Google Scholar 

  33. Dupont, E., Luu-The, V., Labrie, F. & Pelletier, G. Molec. cell. Endocrinol. 74, R7–R10 (1990).

    Article  CAS  Google Scholar 

  34. Martin, F., Perheentupa, J. & Aldercreutz, H. J. Steroid Biochem. 13, 197–201 (1980).

    Article  CAS  Google Scholar 

  35. Labrie, F. Molec. cell. Endocrinol. 78, C113–0118 (1991).

    Article  CAS  Google Scholar 

  36. MacDonald, P.C., Dombroski, R.A. & Casey, L. Endocr. Rev. 12, 372–401 (1991).

    Article  CAS  Google Scholar 

  37. Simard, J. et al. Molec. cell. Endocrinol. 75, 101–110 (1991).

    Article  CAS  Google Scholar 

  38. Zhao, H.F. et al. Endocrinology 127, 3237–3239 (1990).

    Article  CAS  Google Scholar 

  39. Zhao, H.F. et al. J. biol. Chem. 266, 583–593 (1991).

    CAS  PubMed  Google Scholar 

  40. Simard, J., de Launoit, Y. & Labrie, F. J. biol. Chem. 266, 14842–14845 (1991).

    CAS  PubMed  Google Scholar 

  41. de Launoit, Y., Zhao, H.F., Bélanger, A., Labrie, F. & Simard, J. J. biol. Chem. 267, 4513–4517 (1992).

    CAS  PubMed  Google Scholar 

  42. Albrecht, E.D. & Pepe, G.J. Endocr. Rev. 11, 124–150 (1990).

    Article  CAS  Google Scholar 

  43. Rilley, S.C. et al. J. clin. endo. Metab. (in the press).

  44. Kwok, S. et al. Nuc Acids Res. 18, 999–1005 (1990).

    Article  CAS  Google Scholar 

  45. Erlich, H.A., Gelfand, D. & Sninsky, J.J. Science 252, 1643–1651 (1991).

    Article  CAS  Google Scholar 

  46. Kawamoto, T. et al. Proc. natn. Acad. Sci. U.S.A. 89, 1458–1462 (1992).

    Article  CAS  Google Scholar 

  47. Luu-The, V. et al. Molec. Endocrinol. 4, 268–275 (1990).

    Article  CAS  Google Scholar 

  48. Anderson, S.A., Berman, D.M., Jenkins, E.P. & Russell, D.W. Nature 354, 159–161 (1991).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Research Council Group in Molecular Endocrinology, CHUL Research Center and Laval University, Québec, G1V 4G2, Canada

    Eric Rhéaume, Jacques Simard & Fernand Labrie

  2. INSERM U329 and Department of Pediatrics, Université de Lyon and Hôpital Debrousse, Lyon Cedex, 05, France

    Yves Morel, Farida Mebarki & Maguelone G. Forest

  3. Department of Pediatrics, University of Zurich and Kinderspital, 8032, Zurich, Switzerland

    Milo Zachmann

  4. Department of Pediatrics, Division of Pediatric Endocrinology, The New York Hospital-Cornell Medical Center, New York, New York, 10021, USA

    Maria I. New

Authors
  1. Eric Rhéaume
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacques Simard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yves Morel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Farida Mebarki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Milo Zachmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maguelone G. Forest
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria I. New
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fernand Labrie
    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

Rhéaume, E., Simard, J., Morel, Y. et al. Congenital adrenal hyperplasia due to point mutations in the type II 3β–hydroxysteroid dehydrogenase gene. Nat Genet 1, 239–245 (1992). https://doi.org/10.1038/ng0792-239

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0792-239

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