Journal article

Publication year: 2008

Pages: 3584-3588

Journal: The Journal of Clinical Endocrinology & Metabolism

Volume number: 93

Issue number: 9

ISSN: 0021-972X

Open access status: Green

DOI Link: https://doi.org/10.1210/jc.2008-0051

Publisher: Oxford University Press

Abstract: 

Context: Very few patients have been described with isolated 17,20-lyase deficiency who have had their mutations in P450c17 (17 alpha-hydroxylase/17,20-lyase) proven by DNA sequencing and in vitro characterization of the mutations. Most patients with 17,20-lyase deficiency have mutations in the domain of P450c17 that interact with the electron-donating redox partner, P450 oxidoreductase (POR).

Objective: Our objective was to clarify the genetic and functional basis of isolated 17,20-lyase deficiency in familial cases who were previously reported as having 17,20-lyase deficiency.

Patients: Four undervirilized males of an extended Bedouin family were investigated. One of these has previously been reported to carry mutations in the CYP17A1 gene encoding P450c17 causing isolated 17,20-lyase deficiency.

Methods: Serum hormones were evaluated before and after stimulation with ACTH. Urinary steroid metabolites were profiled by gas chromatography-mass spectrometry. Exons 1 and 8 of CYP17A1 previously reported to harbor mutations in one of these patients and all 15 coding exons of POR were sequenced.

Results: Gas chromatography-mass spectrometry (GC-MS) urinary steroid profiling and serum steroid measurements showed combined deficiencies of 17,20-lyase and 21-hydroxylase. Sequencing of exons 1 and 8 of CYP17A1 in two different laboratories showed no mutations. Sequencing of POR showed that all four patients were homozygous for G539R, a previously studied mutation that retains 46% of normal capacity to support the 17 alpha-hydroxylase activity but only 8% of the 17,20-lyase activity of P450c17.

Conclusion: POR deficiency can masquerade clinically as isolated 17,20-lyase deficiency.

Harvard Citation style: Hershkovitz, E., Parvari, R., Wudy, S., Hartmann, M., Gomes, L., Loewental, N., et al. (2008) Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17,20-lyase deficiency, The Journal of Clinical Endocrinology & Metabolism, 93(9), pp. 3584-3588. https://doi.org/10.1210/jc.2008-0051

APA Citation style: Hershkovitz, E., Parvari, R., Wudy, S., Hartmann, M., Gomes, L., Loewental, N., & Miller, W. (2008). Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17,20-lyase deficiency. The Journal of Clinical Endocrinology & Metabolism. 93(9), 3584-3588. https://doi.org/10.1210/jc.2008-0051