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 a lpha-reductase deficiency is becomining increasingly understood. OBJEC TIVE We have performed biochemical and molecular analyses of the 5 alp ha-reductase type 2 gene in a Turkish family with a 5 alpha-reductase deficiency.PATIENT A 46,XY prepubertal Turkish patient with female phe notype showing clitoral hypertrophy, high plasma testosterone and dihy drotestosterone, and normally differentiated and developed testosteron e-dependent internal genitalia. MEASUREMENTS 5 alpha-Reductase activit y, measured by the conversion of H-3-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 enzyma tic 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 i nto 5 alpha-reduced compounds by intact cells and a diminished 5 alpha -reductase activity at acidic pH by sonicated cell extracts strongly s uggested a 5 alpha-reductase type 2 deficiency. Molecular analysis of the 5 alpha-reductase type 2 gene showed a trinucleotide deletion stra ddling codons 156 and 157, responsible for a methionine residue deleti on at position 157 of the protein. The parents' DNA contained both nor mal and deleted alleles. CONCLUSIONS This is the third deletion descri bed in the 5 alpha-reductase type 2 gene. The deleted methionine 157 i s 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 alp ha-reductase activity and abnormal genital development in this patient .