CLINICAL, BIOCHEMICAL, AND GENETIC FINDINGS IN A LARGE PEDIGREE OF MALE AND FEMALE-PATIENTS WITH 5-ALPHA-REDUCTASE-2 DEFICIENCY

The present report describes a cluster of eight patients with male pse udohermaphroditism from a large pedigree with steroid Set-reductase 2 deficiency (5 alpha RD), who reside in Southern Lebanon. They were bor n with unambiguous female external genitalia and reared as girls until puberty, when masculinization occurred, followed by a change of gende r role. Semen analysis and testicular histology revealed maturation ar rest of spermatogenesis, with low sperm count and motility. Determinat ion of urinary 5 alpha- and 5 beta-reduced adrenal steroids enabled us to diagnose the disease in a male patient with the full-blown clinica l syndrome, in another male patient who had undergone bilateral orchid ectomy, and in three female individuals with the biochemical derangeme nt. The female patients were unique in this family with respect to the ir low degree of virilization, but had normal menstrual cycles. Molecu lar genetic studies were performed on DNA extracted from peripheral le ukocytes and from cultured genital skin fibroblasts. The coding sequen ce of the 5 alpha R2 gene (SRD5A2) was studied by exon-specific PCR, s ingle strand conformation polymorphism, and direct sequencing. A homoz ygous point mutation was identified in exon 1, leading to a thymidine for adenine substitution, predicting amino acid substitution of leucin e for glutamine at position 55.