Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5α-reductase 2 deficiency

The present report describes a cluster of eight patients with male pseudohermaphroditism from a large pedigree with steroid 5α-reductase 2 deficiency (5αRD), who reside in Southern Lebanon. They were born with unambiguous female external genitalia and reared as girls until puberty, when masculinization occurred, followed by a change of gender role. Semen analysis and testicular histology revealed maturation arrest of spermatogenesis, with low sperm count and motility. Determination of urinary 5α- and 5β-reduced adrenal steroids enabled us to diagnose the disease in a male patient with the full-blown clinical syndrome, in another male patient who had undergone bilateral orchidectomy, and in three female individuals with the biochemical derangement. The female patients were unique in this family with respect to their low degree of virilization, but had normal menstrual cycles. Molecular genetic studies were performed on DNA extracted from peripheral leukocytes and from cultured genital skin fibroblasts. The coding sequence of the 5αR2 gene (SRD5A2) was studied by exon-specific PCR, single strand conformation polymorphism, and direct sequencing. A homozygous point mutation was identified in exon 1, leading to a thymidine for adenine substitution, predicting amino acid substitution of leucine for glutamine at position 55.