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

Eur J Pediatr. 1996 Jun;155(6):445-51. doi: 10.1007/BF01955179.


Reduced conversion of testosterone (T) to dihydrotestosterone (DHT) results in defective virilization in karyotypic males. Different mutations in the 5 alpha-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 5 alpha-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 5 alpha-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, delta Met157) 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.

Conclusion: 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 rations, and hence to a better discrimination of pathologic results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / deficiency*
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics
  • Amino Acid Sequence / genetics
  • Child
  • Child, Preschool
  • Chorionic Gonadotropin*
  • Consanguinity
  • Dihydrotestosterone / blood*
  • Disorders of Sex Development / enzymology
  • Disorders of Sex Development / genetics*
  • Exons / genetics
  • Homozygote
  • Humans
  • Hypospadias / enzymology
  • Hypospadias / genetics
  • Infant
  • Infant, Newborn
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Karyotyping
  • Male
  • Molecular Sequence Data
  • Phenotype
  • Point Mutation / genetics*
  • Reference Values
  • Testosterone / blood*


  • Chorionic Gonadotropin
  • Isoenzymes
  • Dihydrotestosterone
  • Testosterone
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase