Molecular genetics of steroid 5α-reductase 2 deficiency

Anice E. Thigpen, Daphne L. Davis, Athena Milatovich, Berenice B. Mendonca, Julianne Imperato-McGinley, Jim Griffin III, Uta Francke, Jean D. Wilson, David W Russell

Research output: Contribution to journalArticle

311 Citations (Scopus)

Abstract

Two isozymes of steroid 5α-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 5α-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 5α-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 5α-reductase type 2 gene may be higher than previously thought.

Original languageEnglish (US)
Pages (from-to)799-809
Number of pages11
JournalJournal of Clinical Investigation
Volume90
Issue number3
StatePublished - 1992

Fingerprint

Molecular Biology
Oxidoreductases
Steroids
Heterozygote
Genes
Isoenzymes
XY Disorders of Sex Development 46
Mutation
Genitalia
Chromosomes, Human, Pair 2
Hybrid Cells
Dihydrotestosterone
Homozygote
Mutation Rate
Introns
In Situ Hybridization
Testosterone
Exons
Enzymes

Keywords

  • Androgen metabolism
  • Dihydrotestosterone
  • Human mutations
  • Male pseudohermaphroditism
  • Sexual differentiation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Thigpen, A. E., Davis, D. L., Milatovich, A., Mendonca, B. B., Imperato-McGinley, J., Griffin III, J., ... Russell, D. W. (1992). Molecular genetics of steroid 5α-reductase 2 deficiency. Journal of Clinical Investigation, 90(3), 799-809.

Molecular genetics of steroid 5α-reductase 2 deficiency. / Thigpen, Anice E.; Davis, Daphne L.; Milatovich, Athena; Mendonca, Berenice B.; Imperato-McGinley, Julianne; Griffin III, Jim; Francke, Uta; Wilson, Jean D.; Russell, David W.

In: Journal of Clinical Investigation, Vol. 90, No. 3, 1992, p. 799-809.

Research output: Contribution to journalArticle

Thigpen, AE, Davis, DL, Milatovich, A, Mendonca, BB, Imperato-McGinley, J, Griffin III, J, Francke, U, Wilson, JD & Russell, DW 1992, 'Molecular genetics of steroid 5α-reductase 2 deficiency', Journal of Clinical Investigation, vol. 90, no. 3, pp. 799-809.
Thigpen AE, Davis DL, Milatovich A, Mendonca BB, Imperato-McGinley J, Griffin III J et al. Molecular genetics of steroid 5α-reductase 2 deficiency. Journal of Clinical Investigation. 1992;90(3):799-809.
Thigpen, Anice E. ; Davis, Daphne L. ; Milatovich, Athena ; Mendonca, Berenice B. ; Imperato-McGinley, Julianne ; Griffin III, Jim ; Francke, Uta ; Wilson, Jean D. ; Russell, David W. / Molecular genetics of steroid 5α-reductase 2 deficiency. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 3. pp. 799-809.
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