Molecular genetics of steroid 5 alpha-reductase 2 deficiency.

A E Thigpen; D L Davis; A Milatovich; B B Mendonca; J Imperato-McGinley; J E Griffin; U Francke; J D Wilson; D W Russell

doi:10.1172/JCI115954

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

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

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

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

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

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

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

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

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

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Published in Volume 90, Issue 3 on September 1, 1992
J Clin Invest. 1992;90(3):799–809. https://doi.org/10.1172/JCI115954.
© 1992 The American Society for Clinical Investigation

Published September 1, 1992 - Version history

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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