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Combined 17-Hydroxylase/17,20-Lyase Deficiency due to a 7-Basepair Duplication in the N-Terminal Region of the Cytochrome P450₁₇ (CYP17) Gene^*

Departments of Biochemistry and Obstetrics and Gynecology and the Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center (T. Y., D.S., E.R.S., M.R. W.) Dallas, Texas 75235
The Shibata Clinic (A.S.) Nagoya 460
The Research Institute of Environmental Medicine (N.M.), Nagoya University Nagoya 464–01, Japan

Address requests for reprints to: Dr. Toshihiko Yanase, Departments of Biochemistry and Obstretrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75235.

17-Hydroxylase deficiency is characterized by defects in either or both of the 17-hydroxylase/17,20-lyase activities. We have elucidated the molecular basis of the combined deficiency of these activities in a Japanese female who is genotypically male and the child of a consanguineous marriage. The complete exonic sequence of the patient's CYP17 (P450₁₇) gene revealed a seven-basepair duplication (GCGCACA) in exon 2 which leads to a frame shift and, subsequently, a premature stop codon. Because this stop codon occurs N-terminal to the heme-binding sequence, the presence of this mutation leads to the absence of a functional P450₁₇-protein in adrenal cortex and testis. This, in turn, leads to an absence of sex steroids and excessive secretion of steroids with mineralocorticoid activity and, consequently, female external genitalia and hypertension in this 46XY patient.

^* This work was supported by Research Grant 1084 from The March of Dimes Birth Defects Foundation.

Received September 18, 1989.

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