P450c17 deficiency : Clinical and molecular characterization of six patients

Context: The characteristics of P450c17 deficiency include 46,XY disorder of sex development, hypertension, hypokalemia, and lack of pubertal development. Objective: To better understand this rare enzymatic deficiency, we analyzed the CYP17A1 gene in six affected patients. Design and Patients: We examined six patients, five 46,XY, and one 46,XX (age 9–29 yr) with complete lack of masculinization (female infantile external genitalia, no uterus) and delayed puberty, respectively, and different degrees of hypertension. Main Outcome Measurements: Genotype-phenotype correlation was measured. Results: Four homozygote mutations were identified by direct sequencing of the CYP17A1 gene corresponding to an alanin 302-proline (A302P) exchange; the loss of lysine 327 (K327del); the deletion of glutamate 331 (E331del); and the replacement of arginine 416 with a histidine (R416H). Both P450c17 activities were abolished in all the mutant proteins, except one, when expressed in COS1 cells. The E331del-mutated P450c17 ret...