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


METHODS
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.


METHODS
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.
Boudon
C
C
Centre de Recherches de l'Institut National de la Santé et de la Recherche Médicale, INSERM, Montpellier, France.
Lobaccaro
J M
JM
Lumbroso
S
S
Ogur
G
G
Ocal
G
G
Belon
C
C
Sultan
C
C
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D002478:Cells, Cultured; D003241:Consanguinity; D012734:Disorders of Sex Development / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010290:Parents; D017422:Sequence Analysis, DNA; D012867:Skin / Q000201:enzymology
D007527:Isoenzymes; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase