Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome

Christa E. Flück; Toshihro Tajima; Amit V. Pandey; Wiebke Arlt; Kouji Okuhara; Charles F. Verge; Ethylin Wang Jabs; Berenice B. Mendonça; Kenji Fujieda; Walter L. Miller

doi:10.1038/ng1300

Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome

Christa E. Flück, Toshihro Tajima, Amit V. Pandey, Wiebke Arlt, Kouji Okuhara, Charles F. Verge, Ethylin Wang Jabs, Berenice B. Mendonça, Kenji Fujieda, Walter L. Miller

School of Medicine

Research output: Contribution to journal › Article › peer-review

370 Scopus citations

Abstract

Deficient activities of multiple steroidogenic enzymes have been reported without and with Antley-Bixler syndrome (ABS), but mutations of corresponding cytochrome P450 enzymes have not been found. We identified mutations in POR, encoding P450 oxidoreductase, the obligate electron donor for these enzymes, in a woman with amenorrhea and three children with ABS, even though knock-out of POR is embryonically lethal in mice. Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion.

Original language	English (US)
Pages (from-to)	228-230
Number of pages	3
Journal	Nature Genetics
Volume	36
Issue number	3
DOIs	https://doi.org/10.1038/ng1300
State	Published - Mar 2004

ASJC Scopus subject areas

Genetics(clinical)
Genetics

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title = "Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome",

abstract = "Deficient activities of multiple steroidogenic enzymes have been reported without and with Antley-Bixler syndrome (ABS), but mutations of corresponding cytochrome P450 enzymes have not been found. We identified mutations in POR, encoding P450 oxidoreductase, the obligate electron donor for these enzymes, in a woman with amenorrhea and three children with ABS, even though knock-out of POR is embryonically lethal in mice. Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion.",

author = "Fl{\"u}ck, {Christa E.} and Toshihro Tajima and Pandey, {Amit V.} and Wiebke Arlt and Kouji Okuhara and Verge, {Charles F.} and Jabs, {Ethylin Wang} and Mendon{\c c}a, {Berenice B.} and Kenji Fujieda and Miller, {Walter L.}",

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AU - Flück, Christa E.

AU - Tajima, Toshihro

AU - Pandey, Amit V.

AU - Arlt, Wiebke

AU - Okuhara, Kouji

AU - Verge, Charles F.

AU - Jabs, Ethylin Wang

AU - Mendonça, Berenice B.

AU - Fujieda, Kenji

AU - Miller, Walter L.

PY - 2004/3

Y1 - 2004/3

N2 - Deficient activities of multiple steroidogenic enzymes have been reported without and with Antley-Bixler syndrome (ABS), but mutations of corresponding cytochrome P450 enzymes have not been found. We identified mutations in POR, encoding P450 oxidoreductase, the obligate electron donor for these enzymes, in a woman with amenorrhea and three children with ABS, even though knock-out of POR is embryonically lethal in mice. Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion.

AB - Deficient activities of multiple steroidogenic enzymes have been reported without and with Antley-Bixler syndrome (ABS), but mutations of corresponding cytochrome P450 enzymes have not been found. We identified mutations in POR, encoding P450 oxidoreductase, the obligate electron donor for these enzymes, in a woman with amenorrhea and three children with ABS, even though knock-out of POR is embryonically lethal in mice. Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion.

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Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome

Abstract

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