Molecular genetics of steroid 5 alpha-reductase 2 deficiency
Open accessAbstract
Two isozymes of steroid 5 alpha-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female. The 5 alpha-reductase type 2 gene (gene symbol SRD5A2) was cloned and shown to contain five exons and four introns. The gene was localized to chromosome 2 band p23 by somatic cell hybrid mapping and chromosomal in situ hybridization. Molecular analysis of the SRD5A2 gene resulted in the identification of 18 mutations in 11 homozygotes, 6 compound heterozygotes, and 4 inferred compound heterozygotes from 23 families with 5 alpha-reductase deficiency. 6 apparent recurrent mutations were detected in 19 different ethnic backgrounds. In two patients, the catalytic efficiency of the mutant enzymes correlated with the severity of the disease. The high proportion of compound heterozygotes suggests that the carrier frequency of mutations in the 5 alpha-reductase type 2 gene may be higher than previously thought.
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In chromosomally male individuals, SRD5A2 deficiency presents with undermasculinization, that is, ambiguous genitalia at birth (46,XY DSD).
“In chromosomally male individuals, SRD5A2 deficiency presents with undermasculinization, that is, ambiguous genitalia at birth (46,XY DSD) (56).”
From Steroid Metabolome Analysis in Disorders of Adrenal Steroid Biosynthesis and Metabolism (2019) · cites this paper as [56]
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Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA Polymerase
Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B., & Erlich, H. A. (1988) · Science · doi:10.1126/science.2448875 · Cited by 17,719 · see citing works
Church, G. M., & Gilbert, W. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.7.1991 · Cited by 8,213 · see citing works
[19] Rapid and efficient site-specific mutagenesis without phenotypic selection
Kunkel, T. A., Roberts, J. D., & Zakour, R. A. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)54085-x · Cited by 5,341 · see citing works
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K., & Sekiya, T. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.8.2766 · Cited by 3,589 · see citing works
Orita, M., Suzuki, Y., Sekiya, T., & Hayashi, K. (1989) · Genomics · doi:10.1016/0888-7543(89)90129-8 · Cited by 3,433 · see citing works
Steroid 5α-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism
Imperato-McGinley, J., Guerrero, L., Gautier, T., & Peterson, R. E. (1974) · Science · doi:10.1126/science.186.4170.1213 · Cited by 1,258 · see citing works
Self-citationAndersson, S., Davis, D. L., Dahlbäck, H., Jörnvall, H., & Russell, D. W. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83172-6 · Cited by 1,229 · see citing works
Self-citationLichter, P., Cremer, T., Borden, J., Manuelidis, L., & Ward, D. C. (1988) · Human Genetics · doi:10.1007/bf01790090 · Cited by 1,160 · see citing works
The CpG dinucleotide and human genetic disease
Cooper, D. N., & Youssoufian, H. (1988) · Human Genetics · doi:10.1007/bf00278187 · Cited by 936 · see citing works
Zoller, M. J., & Smith, M. J. (1984) · DNA · doi:10.1089/dna.1.1984.3.479 · Cited by 906 · see citing works
High Resolution of Human Chromosomes
Yunis, J. J. (1976) · Science · doi:10.1126/science.1257746 · Cited by 783 · see citing works
Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism
Andersson, S., Berman, D. M., Jenkins, E. P., & Russell, D. W. (1991) · Nature · doi:10.1038/354159a0 · Cited by 643 · see citing works
Self-citationFamilial Incomplete Male Pseudohermaphroditism, Type 2
Walsh, P. C., Madden, J. D., Harrod, M. J., Goldstein, J. L., MacDonald, P. C., & Wilson, J. D. (1974) · New England Journal of Medicine · doi:10.1056/nejm197410312911806 · Cited by 619 · see citing works
Self-citationAndersson, S., & Russell, D. W. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.10.3640 · Cited by 501 · see citing works
Self-citationGenetic and pharmacological evidence for more than one human steroid 5 alpha-reductase.
Jenkins, E. P., Andersson, S., Imperato-McGinley, J., Wilson, J. D., & Russell, D. W. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115574 · Cited by 395 · see citing works
Self-citationMale pseudohermaphroditism due to steroid 5α-reductase deficiency
Peterson, R. E., Imperato‐McGinley, J., Gautier, T., & Sturla, E. (1977) · The American Journal of Medicine · doi:10.1016/0002-9343(77)90313-8 · Cited by 392 · see citing works
Self-citationDihydrotestosterone Formation in Fetal Tissues of the Rabbit and Rat
WILSON, J. D., & LASNITZKI, I. (1971) · Endocrinology · doi:10.1210/endo-89-3-659 · Cited by 173 · see citing works
Self-citationRapid and Efficient Site-Specific Mutagenesis without Phenotypic Selection
Kunkel, T. A., Roberts, J. D., & Zakour, R. A. (1989) · Elsevier eBooks · doi:10.1016/b978-0-12-765560-4.50038-1 · Cited by 168 · see citing works
Prockop, D. J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55398-9 · Cited by 164 · see citing works
Wilson, J. D. (1978) · Annual Review of Physiology · doi:10.1146/annurev.ph.40.030178.001431 · Cited by 162 · see citing works
Self-citationA cluster of male pseudohermaphrodites with 5α‐reductase deficiency in Papua New Guinea
Imperato‐McGinley, J., Miller, M., Wilson, J. D., Peterson, R. E., Shackleton, C. H. L., & Gajdusek, D. C. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb03769.x · Cited by 161 · see citing works
Self-citationJenkins, E. P., Hsieh, C., Milatovich, A., Normington, K., Berman, D. M., Francke, U., & Russell, D. W. (1991) · Genomics · doi:10.1016/0888-7543(91)90038-g · Cited by 152 · see citing works
Self-citationImperato‐McGinley, J., Peterson, R. E., Gautier, T., & Sturla, E. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90093-1 · Cited by 137 · see citing works
Self-citationBurch, H. B., Bradley, M. E., & Lowry, O. H. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99573-6 · Cited by 116 · see citing works
Imperato‐McGinley, J., Peterson, R. E., Leshin, M., Griffin, J. E., Cooper, G., DRAGHI, S., Berenyi, M. R., & Wilson, J. D. (1980) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-50-1-15 · Cited by 107 · see citing works
Self-citationMoore, R. J., & Wilson, J. D. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33036-3 · Cited by 99 · see citing works
Self-citationThigpen, A. E., & Russell, D. W. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42482-9 · Cited by 95 · see citing works
Self-citationHereditary Male Pseudohermaphroditism Associated with an Unstable Form of 5α-Reductase
Leshin, M., Griffin, J. E., & Wilson, J. D. (1978) · Journal of Clinical Investigation · doi:10.1172/jci109176 · Cited by 95 · see citing works
Self-citationFisher, L. K., Kogut, M. D., MOORE, R. J., Goebelsmann, U., Weitzman, J. J., Isaacs, H., Griffin, J. E., & Wilson, J. D. (1978) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-47-3-653 · Cited by 92 · see citing works
Self-citationChromosomal Mapping of Genes Involved in Growth ControlPreprint
Francke, U., Yang-Feng, T. L., Brissenden, J. E., et al. (1986) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1986.051.01.099 · Cited by 87 · see citing works
Self-citationPrice, P., Wass, J. A. H., Griffin, J. E., Leshin, M., Savage, M. O., Large, D. M., Bu'Lock, D. E., Anderson, D. C., Wilson, J. D., & BESSER, G. M. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111563 · Cited by 85 · see citing works
Self-citationCarpenter, T. O., Imperato‐McGinley, J., Boulware, S. D., WEISS, R. M., Shackleton, C. H. L., Griffin, J. E., & Wilson, J. D. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-2-318 · Cited by 84 · see citing works
Self-citationAlternative Dideoxy Sequencing of Double-Stranded DNA by Cyclic Reactions Using Taq Polymerase
Lee, J. S. (1991) · DNA and Cell Biology · doi:10.1089/dna.1991.10.67 · Cited by 73 · see citing works
Characterization of the Testicular Abnormality in 5a-Reductase Deficiency*
Johnson, L. W., George, F. W., Neaves, W. B., Rosenthal, I. M., CHRISTENSEN, R. A., Dechristoforo, A., Schweikert, H., Sauer, M. V., Leshin, M., Griffin, J. E., et al. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-5-1091 · Cited by 61 · see citing works
Self-citationMilatovich, A., Travis, A., Grosschedl, R., et al. (1991) · Genomics · doi:10.1016/0888-7543(91)90030-i · Cited by 56 · see citing works
Self-citationFAMILIAL MALE PSEUDOHERMAPHRODITISM DUE TO DEFICIENCY OF 5α‐REDUCTASE
Savage, M. O., Preece, M. A., Jeffcoate, S. L., Ransley, P. G., Rumsby, G., Mansfield, M. D., & Williams, D. I. (1980) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1980.tb02727.x · Cited by 41 · see citing works
Peterson, R. E., Imperato‐McGinley, J., Gautier, T., & Shackleton, C. H. L. (1985) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1985.tb00181.x · Cited by 39 · see citing works
Self-citationIn VitroSteroid Metabolic Studies in Testicular 17β-Reduction Deficiency
Goebelsmann, U., HALL, T. D., Paul, W. L., & Stanczyk, F. Z. (1975) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-41-6-1136 · Cited by 27 · see citing works
A rapid method for preparing phage λ DNA from agar plate lysates
Xu, S.-Y. (1986) · Gene Analysis Techniques · doi:10.1016/0735-0651(86)90009-9 · Cited by 22 · see citing works
The endocrine control of sexual differentiation.
Jd, W. (1986) · PubMed · Cited by 18 · see citing works
Pseudovaginal Perineoscrotal Hypospadias
Bartsch, G., Decristoforo, C., & Schweikert, U. (1987) · European Urology · doi:10.1159/000472829 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Griffin, J. E., and J. D. Wilson. 1989. The androgen resistance syndromes: 5a-reductase deficiency, testicular feminization, and related disorders. In The Metabolic Basis of Inherited Disease. C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, editors. McGraw-Hill, Inc., New York. 1919-1944.
- Andersson, S., and D. W. Russell. 1990. Structural and biochemical prop- erties of cloned and expressed human and rat steroid Sa-reductases. Proc. Natl. Acad. Sci. USA. 87:3640-3644.
- Francke, U., T. L. Yang-Feng, J. E. Brissenden, and A. Ullrich. 1986. Chromosomal mapping ofgenes involved in growth control. Cold Spring Harbor Symposium on Quantitative Biology, Cold Spring Harbor Laboratory, NY. 51:855-866.
Cited by
Sorted by citations
Neurosteroids: biosynthesis and function of these novel neuromodulators
Compagnone, N. A., & Mellon, S. H. (2000) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1999.0188 · Cited by 820 · see citing works
Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.
Thigpen, A. E., Silver, R. I., Guileyardo, J. M., Casey, M. L., McConnell, J. D., & Russell, D. W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116665 · Cited by 727 · see citing works
Self-citationMale pseudohermaphroditism caused by mutations of testicular 17β-hydroxysteroid dehydrogenase 3
Geissler, W. M., Davis, D. L., Wu, L., Bradshaw, K. D., Patel, S., Mendonca, B. B., Elliston, K. O., Wilson, J. D., Russell, D. W., & Andersson, S. (1994) · Nature Genetics · doi:10.1038/ng0594-34 · Cited by 570 · see citing works
Self-citationSteroid Metabolome Analysis in Disorders of Adrenal Steroid Biosynthesis and Metabolism
Storbeck, K.-H., Schiffer, L., Baranowski, E. S., Chortis, V., Prete, A., Barnard, L., Gilligan, L. C., Taylor, A. E., Idkowiak, J., Arlt, W., et al. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00262 · Cited by 141 · see citing works
Characterization, Expression, and Immunohistochemical Localization of 5α-Reductase in Human Skin
Luu-The, V., Sugimoto, Y., Puy, L., Labrie, Y., Solache, I. L., Singh, M., & Labrie, F. (1994) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12371766 · Cited by 118 · see citing works
Molecular aspects of sexual differentiation of the rodent brain
McCarthy, M. M. (1994) · Psychoneuroendocrinology · doi:10.1016/0306-4530(94)90029-9 · Cited by 94 · see citing works
5α-Reduced C21 steroids are substrates for human cytochrome P450c17
Gupta, M. K., Guryev, O. L., & Auchus, R. J. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.07.003 · Cited by 84 · see citing works
5α-Reductases in human physiology: an unfolding story
Traish, A. M. (2012) · Endocrine Practice · doi:10.4158/ep12108.ra · Cited by 57 · see citing works
Cations Inhibit Specifically Type I 5α-Reductase Found in Human Skin
Sugimoto, Y., López-Solache, I., Labrie, F., & Luu-The, V. A. N. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12606985 · Cited by 53 · see citing works
Rogers, S. L., Hughes, B. A., Jones, C. A., Freedman, L., Smart, K., Taylor, N., Stewart, P. M., Shackleton, C. H. L., Krone, N. P., Blissett, J., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3254 · Cited by 25 · see citing works
- Authors
- Thigpen, A. E., Davis, D. L., Milatovich, A., Mendonca, B. B., Imperato-McGinley, J., Griffin, J. E., Francke, U., Wilson, J. D., & Russell, D. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Cornell University (US)
- Universidade de São Paulo (BR)
- Stanford University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1992-09-01
- Volume
- 90
- Issue
- 3
- Pages
- 799-809
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC329933
- OpenAlex
- W2079363713
- Cited by
- 422
- References
- 43
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 12 · 2023: 23 · 2022: 10 · 2021: 6 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 7 · 2016: 11 · 2015: 13 · 2014: 9 · 2013: 8 · 2012: 6
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Welch Foundation
- National Institutes of Health (5r01gm043753-07, 5r01dk003892-40, 5r01hg000298-17)
- National Human Genome Research Institute (HG 00298)
- National Institute of General Medical Sciences (GM-43753)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-03892)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- SRD5A2 gene, gene cloning, gene mapping, genetic mutations, compound heterozygosity, 46,XY disorders of sex development, carrier frequency, enzyme catalytic efficiency, disease severity
- MeSH terms
- Base Sequence, Chromosome Mapping, Female, Heterozygote, Humans, Hydrogen-Ion Concentration, Male, Molecular Sequence Data, Mutation, Disorders of Sex Development, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
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