Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• European journal of pediatrics, 1996-06, Vol.155 (6), p.445

Ort / Verlag

Berlin: Springer Nature B.V

Erscheinungsjahr

1996

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• 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 (Gly^sub 196^-Ser, Arg^sub 227^-Gln and Ala^sub 228^-Thr) were identified in the patients. In contrast, in the DNA from 100 phenotypically normal males only two heterozygous abnormalities (Ile^sub 196^-Ile, [Delta]Met^sub 157^) 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/m^sup 2^ 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.