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

*Corresponding author for this work
59 Citations (Scopus)

Abstract

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. 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 ratios, and hence to a better discrimination of pathologic results.

Original languageEnglish
JournalEuropean Journal of Pediatrics
Volume155
Issue number6
Pages (from-to)445-451
Number of pages7
ISSN0340-6199
DOIs
Publication statusPublished - 1996

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

Fingerprint

Dive into the research topics of 'Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5α-reductase deficiency'. Together they form a unique fingerprint.

Cite this