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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 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
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).
Morel, Y. & Miller, W.L. Adv. hum. Genet. 20, 1–68 (1991).
Zachmann, M., Tassinari, D. & Prader, A. J. clin. Endocrinol. Metab. 56, 222–229 (1983).
White, P.C. et al. J. clin. Invest. 87, 1664–1667 (1991).
Yanase, T., Simpson, E.R. & Waterman, M.R. Endocr. Rev. 12, 91–108 (1991).
Bongiovanni, A.M. Fertil. Steril. 35, 599 (1981).
Luu-The, V. et al. Molec. Endocrinol. 3, 1310–1312 (1989).
Lachance, Y. et al. J. biol. Chem. 265, 20469–20475 (1990).
Rhéaume, E. et al. Molec. Endocrinol. 5, 1147–1157 (1991).
Lachance, Y. et al. DNA cell. Biol. 10, 701–711 (1991).
Bongiovanni, A.M. & Kellenbenz, G. J. clin. Invest 41, 2086–2092 (1962).
Parks, G.A., Bermudez, J.A., Anast, C.S., Bongiovanni, A.M. & New, M.I. J. clin. Endocrinol. 33, 269–278 (1971).
Schneider, G., Genel, M., Bongiovanni, A.M., Goldman, A.S. & Rosenfield, R.L. J. clin. Invest. 55, 681–690 (1975).
Zachmann, M., Völlmin, A., Mürset, G., Curtius, H.-C.H. & Prader, A. J. clin. Endocr. 30, 719–726 (1970).
Zachmann, M., Forest, M.G. & de Peretti, E. Horm. Res. 11, 292–302 (1979).
Cara, J.F., Moshang, T., Bongiovanni, A.M., Marx, B.S. New Engl. J. Med. 313, 618–621 (1985).
. de Peretti, E. & Forest, M.G. Hormone Res. 16, 10–22 (1982).
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).
Pang, S. et al. J. clin. Endocrinol. Metab. 56, 808–818 (1983).
Gendrel, D., Chaussain, J.L., Roger, M. & Job, J.C. Arch. Franç. Pédiat. 36, 647–655 (1975).
Rosenfield, R.L. et al. J. clin. Endocrinol. Metab. 51, 345–353 (1980).
Mendoca, B.B. et al. J. Steroid Biochem. 28, 669–675 (1987).
Bérubé, D., Luu-The, V., Lachance, Y., Gagné, R. & Labrie, F. Cytogen. Cell. Genet. 52, 199–200 (1989).
Zachmann, M., Kempken, B., Anner, I. & Pezzoli, V. Ped. Res. 24, 543 (1988).
Rhéaume, E., Leblanc, J.F., Lachance, Y., Labrie, F. & Simard, J., Hum. Genet. 87, 753–754 (1991).
Rhéaume, E., Sirois, I., Labrie, F. & Simard, J. Nucl. Acid Res. 19, 6060 (1991).
Rosenfield, R.L., de Niepomniszsze, A.B., Kenny, F.M. & Genel, M. J. clin. endo. Metab. 39, 370–374 (1974).
Goldman, A.S., Yakovac, W.C. & Bongiovanni, A.M. J. clin. endo. Metab. 26, 14–22 (1966).
Milewich, L. et al. J. clin. endo. Metab. 73, 1134–1140 (1991).
Dupont, E., Luu-The, V., Labrie, F. & Pelletier, G. J. Androl. 12, 161–164 (1990).
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).
Dupont, E., Labrie, F., Luu-The, V. & Pelletier, G. J. clin. Endo. Metab. 74, 994–998 (1992).
Dupont, E., Luu-The, V., Labrie, F. & Pelletier, G. Molec. cell. Endocrinol. 74, R7–R10 (1990).
Martin, F., Perheentupa, J. & Aldercreutz, H. J. Steroid Biochem. 13, 197–201 (1980).
Labrie, F. Molec. cell. Endocrinol. 78, C113–0118 (1991).
MacDonald, P.C., Dombroski, R.A. & Casey, L. Endocr. Rev. 12, 372–401 (1991).
Simard, J. et al. Molec. cell. Endocrinol. 75, 101–110 (1991).
Zhao, H.F. et al. Endocrinology 127, 3237–3239 (1990).
Zhao, H.F. et al. J. biol. Chem. 266, 583–593 (1991).
Simard, J., de Launoit, Y. & Labrie, F. J. biol. Chem. 266, 14842–14845 (1991).
de Launoit, Y., Zhao, H.F., Bélanger, A., Labrie, F. & Simard, J. J. biol. Chem. 267, 4513–4517 (1992).
Albrecht, E.D. & Pepe, G.J. Endocr. Rev. 11, 124–150 (1990).
Rilley, S.C. et al. J. clin. endo. Metab. (in the press).
Kwok, S. et al. Nuc Acids Res. 18, 999–1005 (1990).
Erlich, H.A., Gelfand, D. & Sninsky, J.J. Science 252, 1643–1651 (1991).
Kawamoto, T. et al. Proc. natn. Acad. Sci. U.S.A. 89, 1458–1462 (1992).
Luu-The, V. et al. Molec. Endocrinol. 4, 268–275 (1990).
Anderson, S.A., Berman, D.M., Jenkins, E.P. & Russell, D.W. Nature 354, 159–161 (1991).
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0792-239
This article is cited by
-
The interplay of renal potassium and sodium handling in blood pressure regulation: critical role of the WNK-SPAK-NCC pathway
Journal of Human Hypertension (2019)
-
Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency
Endocrine (2019)
-
Gynaecomastia—pathophysiology, diagnosis and treatment
Nature Reviews Endocrinology (2014)
-
Störungen der Bildung von Sexualsteroidhormonen und Hyperandrogenämie bei der Frau
Medizinische Genetik (2011)
-
The genetic basis of adrenal gland weight and structure in BXD recombinant inbred mice
Mammalian Genome (2011)