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.

• Authors: 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
• Journal: Nature genetics (Nat Genet) Vol. 36 Issue 3 Pg. 228-30 (Mar 2004) ISSN: 1061-4036 [Print] United States
• PMID: 14758361 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Gonadal Steroid Hormones
• Ketone Oxidoreductases
• Pyruvate Synthase
• NADPH-Ferrihemoprotein Reductase

Topics

• Craniosynostoses (genetics)
• Female
• Gonadal Steroid Hormones (biosynthesis)
• Humans
• Ketone Oxidoreductases (genetics)
• Mutation
• NADPH-Ferrihemoprotein Reductase (genetics)
• Pyruvate Synthase
• Syndrome
• Synostosis (genetics)