A genetic disorder in cytochrome P450c17 results in 17 alpha-hydroxylase/17,20-lyase deficiency. In the present study, a Japanese patient with 17 alpha-hydroxylase/17,20-lyase deficiency underwent molecular analysis. The patient presented with complete female genitalia with a 46,XY karyotype, absent pubertal development, and hypertension. the exons and exon-intron boundaries of P450c17 genetic region were amplified and sequenced. DNA sequencing revealed a compound heterozygous mutation. One allele showed a G to A transition corresponding to a premature termination codon at tryptophane in codon 17 (W17X). The other allele showed a G to T substitution at the fifth nucleotide from the splice donor site in intron 2 (436 + 5G --> T). W17X was found in one allele of the father, and 436 + 5G --> T was found in one allele of the mother. A previous report presented a patient with 17 alpha-hydroxylase/17,20-lyase deficiency who was homozygous for W17X. However, the present case is a novel 436 + 5G --> T mutation. Reverse transcription-PCR analysis using total ribonucleic acid isolated from the testes of the patient revealed that an intron 2 donor site mutation caused abnormal splicing, such that exon 2 was spliced with intron 2. Skipping the exon alters the translational reading frame of exon 3 and introduces a premature termination codon. In semiquantitative analysis, the majority of the transcript for 436 + 5G --> T skips exon 2. The present findings indicate that in this patient, 17 alpha-hydroxylase/17,20-lyase deficiency was caused by the compound heterozygous mutation of exon and splice site mutation in cytochrome P450c17 gene.
