查看文章

Human male sexual differentiation requires production of fetal testicular testosterone, whose biosynthesis requires steroid 17,20-lyase activity^1,2. Patients with putative isolated 17,20-lyase deficiency have been reported^3,4. The existence of true isolated 17,20-lyase deficiency, however, has been questioned because 17α-hydroxylase and 17,20-lyase activities are catalyzed by a single enzyme^5–8, microsomal cytochrome P450c17, and because the index case of apparent isolated 17,20-lyase deficiency had combined deficiencies of both activities^9,10. We studied two patients with clinical and hormonal findings suggestive of isolated 17,20-lyase deficiency. We found two patients homozygous for substitution mutations in CYP17, the gene encoding P450c17. When expressed in COS-1 cells, the mutants retained 17α-hydroxylase activity but had minimal 17,20-lyase activity. Substrate competition experiments …