Identification of a novel splicing mutation and 1-bp deletion in the 17alpha-hydroxylase gene of Japanese patients with 17alpha-hydroxylase deficiency

Hum Genet. 1998 Jun;102(6):635-9. doi: 10.1007/s004390050754.


We report studies of two unrelated Japanese patients with 17alpha-hydroxylase deficiency caused by mutations of the 17alpha-hydroxylase (CYP17) gene. We amplified all eight exons of the CYP17 gene, including the exon-intron boundaries, by the polymerase chain reaction and determined their nucleotide sequences. Patient 1 had novel, compound heterozygous mutations of the CYP17 gene. One mutant allele had a guanine to thymine transversion at position +5 in the splice donor site of intron 2. This splice-site mutation caused exon 2 skipping, as shown by in vitro minigene expression analysis of an allelic construct, resulting in a frameshift and introducing a premature stop codon (TAG) 60 bp downstream from the exon 1-3 boundary. The other allele had a missense mutation of His (CAC) to Leu (CTC) at codon 373 in exon 6. These two mutations abolished the 17alpha-hydroxylase and 17,20-lyase activities. Restriction fragment length polymorphism (RFLP) analysis with a mismatch oligonucleotide showed that the patient's mother and brother carried the splice-site mutation, but not the missense mutation. Patient 2 was homozygous for a novel 1-bp deletion (cytosine) at codon 131 in exon 2. This 1-bp deletion produces a frameshift in translation and introduces a premature stop codon (TAG) proximal to the highly conserved heme iron-binding cysteine at codon 442 in microsomal cytochrome P450 steroid 17alpha-hydroxylase (P450c17). RFLP analysis showed that the mother was heterozygous for the mutation.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adrenal Hyperplasia, Congenital
  • Adult
  • DNA Mutational Analysis
  • Female
  • Gene Expression
  • Humans
  • Japan
  • Mutation*
  • Polymorphism, Restriction Fragment Length
  • RNA Splicing / genetics*
  • Sequence Analysis, DNA
  • Sequence Deletion*
  • Steroid 17-alpha-Hydroxylase / genetics*


  • Steroid 17-alpha-Hydroxylase