[New compound heterozygous mutation causes partial combined 17 alpha-hydroxylase/17,20-lyase deficiency].

To investigate the CYP17A1 gene mutations in a Chinese 46,XX patient with partial combined 17 alpha-hydroxylase/17,20-lyase deficiency.Clinical data were retrospectively analyzed. The genomic DNA of the patient and her parents was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then subclone sequenced. Sequencing results were compared to the established human CYP17A1 sequence.The patient was new compound heterozygous of 5994-5995 delAT/7541 C>T. The mutation 5994-5995 del AT, causing amino acid I259H, 274X, was proposed to result early truncated protein which was lack of the activity center site of P450C17, whereas missense mutation 7541 C>T causing A398V did not lie in the active site of the enzyme according to the computer model of human P450C17. The 46, XX case had irregular menstruation and slightly hypertension and hypokalemia. The ACTH stimulating test as well as the result of the sex hormones suggested that there was partial 17 alpha-hydroxylase/17, 20-lyase enzyme activities in the adrenal and sexual gland. We speculate that A398V might conserve partial of the enzyme's activities. The genotype was coincident with phenotype.More study should be done to have better understanding of the function of the mutated P450C17 enzymes.