New compound heterozygous mutation in the CYP17 gene in a 46,XY girl with 17 alpha-hydroxylase/17,20-lyase deficiency

Horm Res. 2001;55(3):141-6. doi: 10.1159/000049986.


Background: 17alpha-Hydroxylase/17,20-lyase deficiency is caused by a defect of P450c17 which catalyzes both 17alpha-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads.

Results: In the present study, we analyzed the CYP17 gene in a Japanese patient with 17alpha-hydroxylase/17,20-lyase deficiency. The patient was a phenotypic girl and referred to us for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue. The karyotype was 46,XY. At 6 years of age, hypertension was clearly recognized and the patient was diagnosed as having 17alpha-hydroxylase/17,20-lyase deficiency based on the clinical and laboratory findings. Analysis of the CYP17 gene revealed a compound heterozygous mutation. One mutation was an undescribed single nucleotide deletion at codon 247 in exon 4 (CTT to CT: 247delT) and the other was a missense mutation resulting in a substitution of His to Leu at codon 373 in exon 6 (CAC to CTC: H373L), which has been previously shown to abolish both 17alpha-hydroxylase and 17,20-lyase activities. The functional expression study of the 247delT mutant showed that this 247delT mutation completely eliminates both 17alpha-hydroxylase and 17,20-lyase activities.

Conclusions: Together, these results indicate that the patient is a compound heterozygote for the mutation of the CYP17 gene (247delT and H373L) and that these mutations inactivate both 17alpha-hydroxylase and 17,20-lyase activities and give rise to clinically manifest 17alpha-hydroxylase/17,20-lyase deficiency.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital*
  • Animals
  • COS Cells
  • Cell Line
  • Child, Preschool
  • DNA Mutational Analysis / methods
  • Female
  • Gene Expression Regulation, Enzymologic / genetics
  • Genetic Carrier Screening*
  • Gonadal Dysgenesis, 46,XY / enzymology*
  • Gonadal Dysgenesis, 46,XY / genetics*
  • Humans
  • Mutation / genetics*
  • Phenotype
  • Steroid 17-alpha-Hydroxylase / biosynthesis
  • Steroid 17-alpha-Hydroxylase / genetics*


  • Steroid 17-alpha-Hydroxylase