Phenotype-genotype correlation in eight Chinese 17α-hydroxylase/17,20 lyase-deficiency patients with five novel mutations of CYP17A1 gene

Jun Yang, Bin Cui, Shouyue Sun, Tieliu Shi, Siyuan Zheng, Yufang Bi, Jianmin Liu, Yongju Zhao, Jialun Chen, Guang Ning, Xiaoying Li

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Context: P450c17 deficiency (17OHD), caused by mutation in CYP17A1 gene, is characterized by severe hypertension-hypokalemia, sexual infantilism in females, and pseudohermaphroditism in males. We investigated eight Chinese 17OHD patients with five novel mutations of CYP17A1 gene and analyzed phenotype-genotype correlation in a patient with regular menses and seven others with classic presentations by in vitro expression and computer modeling. Objective: The objective of the study was to explore the phenotype-genotype correlation in patients with subtle and classic manifestations. Subjects and Methods: Eight patients with 17OHD from seven families were diagnosed according to clinical manifestations and basal hormone assays. The CYP17A1 gene was amplified and sequenced. Haplotyping analysis was performed to determine a common ancestor for those subjects with a frequent mutation 1517_1525del. In vitro enzymatic activities assay and computer modeling were used to analyze the phenotype-genotype correlation. Results: Five novel CYP17A1 mutations, homozygous D487_F489del (1517_1525del) and F453S, combined compound Y329K and 1047del, P434L and V310_W313del, and R416C and D487_F489del were identified. Haplotyping showed that 1517_1525del might be inherited from a common ancestor. Compared with the mutations in patients with classical manifestations, F453S in the patient with regular menses, occasional hypertension, and hypokalemia showed a partially reduced 17α-hydroxylase (29% of those of wild type) and a minor protein conformational change. Conclusion: The clinical manifestations in patients with 17OHD correlate with CYP17A1 mutations and enzymatic activities by in vitro enzyme assay and computer modeling. F453S mutation results in partially reduced enzymatic activities and a subtle phenotype. The prevalent mutation 1517_1525del in Chinese 17OHD patients might be a founder effect.

Original languageEnglish (US)
Pages (from-to)3619-3625
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number9
StatePublished - 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, medical
  • Endocrinology
  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism


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