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Male pseudohermaphroditism caused by mutations of testicular 17β–hydroxysteroid dehydrogenase 3

Nature Genetics volume 7, pages 34–39 (1994)Cite this article

Abstract

Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17β–hydroxysteroid dehydrogenase (17β–HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17β–HSD type 3 isozyme that shares 23% sequence identity with other 1 7β–HSD enzymes, uses NADPH as a cofactor, and is expressed predominantly in the testes. The 17βHSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17βHSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17β–HSD type 3 isozyme.

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Authors and Affiliations

  1. Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    Wayne M. Geissler, Ling Wu, Sushma Patel & Stefan Andersson

  2. Department of Biological Data, Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    Keith O. Elliston

  3. Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA

    Daphne L. Davis & David W. Russell

  4. Departments of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA

    Karen D. Bradshaw

  5. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA

    Jean D. Wilson

  6. Department of Medicine, University of São Paulo, Caixa Postal 8091, São Paulo, Brazil

    Berenice B. Mendonca

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  1. Wayne M. Geissler
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  2. Daphne L. Davis
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  7. Keith O. Elliston
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  8. Jean D. Wilson
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  10. Stefan Andersson
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Geissler, W., Davis, D., Wu, L. et al. Male pseudohermaphroditism caused by mutations of testicular 17β–hydroxysteroid dehydrogenase 3. Nat Genet 7, 34–39 (1994). https://doi.org/10.1038/ng0594-34

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  • DOI: https://doi.org/10.1038/ng0594-34

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