European Journal of Pediatrics

, Volume 155, Issue 6, pp 445–451 | Cite as

Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5α-reductase deficiency

  • Olaf Hiort
  • Holger Willenbring
  • Norbert Albers
  • Wolfgang Hecker
  • Jürgen Engert
  • Leif Dibbelt
  • Gernot H. G. Sinnecker


Reduced conversion of testosterone (T) to dihydrotestosterone (DHT) results in defective virilization in karyotypic males. Different mutations in the 5α-reductase type 2 gene cause the phenotypic variability of the disease. In this report we describe four prepubertal patients with a predominantly male phenotype who carry homozygous point mutations in the 5α-reductase type 2 gene and address the specific T and DHT response to different human chorionic gonadotropin (hCG) stimulation tests. For molecular genetic analysis, DNA from peripheral blood leucocytes was studied. The coding region of the 5α-reductase type 2 gene was characterized by exon-specific polymerase chain reaction amplification, non-radioactive single strand polymorphism analysis, and direct sequencing. Three different homozygous point mutations (Gly196−Ser, Arg227−Gln and Ala228−Thr) were identified in the patients. In contrast, in the DNA from 100 phenotypically normal males only two heterozygous abnormalities (Ile196−Ile, ΔMet157) were characterized. For hormonal studies, T and DHT were measured in serum before and after hCG stimulation employing different protocols. HCG stimulation with 5000 IU/m2 once and prolonged stimulation with seven injections of 1500 IU hCG per single dose every other day were used.


While abnormal T/DHT ratios were identified with both hCG protocols in the patients, prolonged stimulation lead to higher T values and to higher T/DHT ratios, and hence to a better discrimination of pathologic results.

Key words

Male pseudohermaphroditism Hypospadias 5α-Reductase 2 Single strand conformation polymorphism Human chorionic gonadotropin 





human chorionic gonadotropin


polymerase chain reaction


sex hormone-binding globulin


single strand conformation polymorphism




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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Olaf Hiort
    • 1
  • Holger Willenbring
    • 1
  • Norbert Albers
    • 2
  • Wolfgang Hecker
    • 3
  • Jürgen Engert
    • 4
  • Leif Dibbelt
    • 5
  • Gernot H. G. Sinnecker
    • 1
  1. 1.Department of PaediatricsMedical University of LübeckLübeckGermany
  2. 2.Department of PaediatricsMedical University of HannoverHannoverGermany
  3. 3.Department of PaediatricsOlga HospitalStuttgartGermany
  4. 4.Department of Paediatric SurgeryRuhr-University Bochum, MarienhospitalHerneGermany
  5. 5.Institute for Biochemical EndocrinologyMedical University of LübeckLübeckGermany

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