Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome.
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.
Flück
Christa E
CE
Department of Pediatrics, University of California San Francisco, San Francisco, California 94143-0978, USA.
Tajima
Toshihro
T
Pandey
Amit V
AV
Arlt
Wiebke
W
Okuhara
Kouji
K
Verge
Charles F
CF
Jabs
Ethylin Wang
EW
Mendonça
Berenice B
BB
Fujieda
Kenji
K
Miller
Walter L
WL
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*
D012739:Gonadal Steroid Hormones; D007658:Ketone Oxidoreductases; D050743:Pyruvate Synthase; D009251:NADPH-Ferrihemoprotein Reductase