A new deletion of the 5 alpha-reductase type 2 gene in a Turkish family with 5 alpha-reductase deficiency.

Abstract

UNLABELLED:

The molecular basis for male pseudohermaphroditism produced by the 5 alpha-reductase deficiency is becoming increasingly understood.

OBJECTIVE:

We have performed biochemical and molecular analyses of the 5 alpha-reductase type 2 gene in a Turkish family with a 5 alpha-reductase deficiency.

PATIENT:

A 46,XY prepubertal Turkish patient with female phenotype showing clitoral hypertrophy, high plasma testosterone and dihydrotestosterone, and normally differentiated and developed testosterone-dependent internal genitalia.

MEASUREMENTS:

5 alpha-Reductase activity, measured by the conversion of 3H-T into 5 alpha-reduced compounds, was determined from cultured genital skin fibroblasts by both intact monolayer assay and cell-free extracts at various pH values. The five exons of the 5 alpha-reductase type 2 gene were sequenced after enzymatic amplification (PCR) of the patient's genomic DNA. Labelled PCR of the consanguineous parents' DNA was submitted to electrophoresis on a sequencing gel.

RESULTS:

A marked decrease in the transformation of T into 5 alpha-reduced compounds by intact cells and a diminished 5 alpha-reductase activity at acidic pH by sonicated cell extracts strongly suggested a 5 alpha-reductase type 2 deficiency. Molecular analysis of the 5 alpha-reductase type-2 gene showed a trinucleotide deletion straddling codons 156 and 157, responsible for a methionine residue deletion at position 157 of the protein. The parents' DNA contained both normal and deleted alleles.

CONCLUSIONS:

This is the third deletion described in the 5 alpha-reductase type 2 gene. The deleted methionine 157 is conserved in both types 1 and 2 of human and rat 5 alpha-reductase, which suggests its crucial role in the functioning of the enzyme. This gene rearrangement was thus clearly responsible for the reduced 5 alpha-reductase activity and abnormal genital development in this patient.

• Authors: C Boudon, J M Lobaccaro, S Lumbroso, G Ogur, G Ocal, C Belon, C Sultan
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 43 Issue 2 Pg. 183-8 (Aug 1995) ISSN: 0300-0664 [Print] England
• PMID: 7554313 (Publication Type: Journal Article)

Chemical References

• Isoenzymes
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Topics

• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (deficiency, genetics)
• Cells, Cultured
• Consanguinity
• Disorders of Sex Development (enzymology)
• Female
• Fibroblasts (enzymology)
• Gene Deletion
• Humans
• Infant
• Isoenzymes (deficiency, genetics)
• Male
• Molecular Sequence Data
• Parents
• Sequence Analysis, DNA
• Skin (enzymology)