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.
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, California 94143-0978, USA.
authors.forename: Christa E
authors.initials: CE
authors.lastname: Flück
authors.forename: Toshihro
authors.initials: T
authors.lastname: Tajima
authors.forename: Amit V
authors.initials: AV
authors.lastname: Pandey
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.forename: Kouji
authors.initials: K
authors.lastname: Okuhara
authors.forename: Charles F
authors.initials: CF
authors.lastname: Verge
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonça
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
authors.forename: Walter L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D003398:Craniosynostoses / Q000235:genetics; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D006801:Humans; D007658:Ketone Oxidoreductases / Q000235:genetics*; D009154:Mutation; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics*; D050743:Pyruvate Synthase; D013577:Syndrome; D013580:Synostosis / Q000235:genetics*
chemical_list: D012739:Gonadal Steroid Hormones; D007658:Ketone Oxidoreductases; D050743:Pyruvate Synthase; D009251:NADPH-Ferrihemoprotein Reductase