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Brief Communication
Nature Genetics  36, 228 - 230 (2004)
Published online: 1 February 2004; | doi:10.1038/ng1300

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

Christa E Flück1, 7, Toshihro Tajima2, 7, Amit V Pandey1, Wiebke Arlt1, Kouji Okuhara2, Charles F Verge3, Ethylin Wang Jabs4, Berenice B Mendonça5, Kenji Fujieda6 & Walter L Miller1

1  Department of Pediatrics, University of California San Francisco, San Francisco, California 94143-0978, USA.

2  Department of Pediatrics, Hokkaido University, Sapporo, Japan.

3  Department of Endocrinology, Sydney Children's Hospital, Randwick, Australia.

4  Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.

5  Department of Medicine, Hospital das Clinicas, University of São Paulo, São Paulo, Brazil.

6  Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan.

7  These authors contributed equally to this work.

Correspondence should be addressed to Walter L Miller wlmlab@itsa.ucsf.edu
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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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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