title: Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients.
abstract: Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ7-sterol reductase, DHCR7, EC 1.3.1.21) leading to a build-up of the cholesterol precursor 7-dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology. We have identified a novel hydroxy-8-dehydrocholesterol, which is either 24- or 25-hydroxy-8-dehydrocholesterol and also the known metabolites 26-hydroxy-8-dehydrocholesterol, 4-hydroxy-7-dehydrocholesterol, 3β,5α-dihydroxycholest-7-en-6-one and 7α,8α-epoxycholesterol. None of these metabolites are detected in control plasma at quantifiable levels (0.5ng/mL).
authors.affiliation: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.
authors.forename: William J
authors.initials: WJ
authors.lastname: Griffiths
authors.affiliation: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
authors.forename: Jonas
authors.initials: J
authors.lastname: Abdel-Khalik
authors.affiliation: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crick
authors.affiliation: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Ogundare
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Cedric H
authors.initials: CH
authors.lastname: Shackleton
authors.affiliation: Centre for Translational Omics, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Karin
authors.initials: K
authors.lastname: Tuschl
authors.affiliation: Centre for Translational Omics, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Mei Kwun
authors.initials: MK
authors.lastname: Kwok
authors.affiliation: Stem Cell & Neurotherapies, Manchester Centre for Genomic Medicine, University of Manchester, Manchester M13 1PT, UK.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Bigger
authors.affiliation: Willink Biochemical Genetics Unit, Genetic Medicine, St. Mary's Hospital, Oxford Road, Manchester M13 9WL, UK.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Morris
authors.affiliation: Tokyo Medical University, Ibaraki Medical Center, 3-20-1Chuoh, Ami, Ibaraki 300-0395, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Honda
authors.affiliation: Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Libin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Ned A
authors.initials: NA
authors.lastname: Porter
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
authors.affiliation: Centre for Translational Omics, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Clayton
authors.affiliation: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: y.wang@swansea.ac.uk.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002775:Cholestadienols / Q000097:blood; D003684:Dehydrocholesterols / Q000097:blood; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000072376:Oxysterols / Q000097:blood*; D010949:Plasma / Q000737:chemistry; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood*; D013261:Sterols / Q000097:blood*
chemical_list: D002775:Cholestadienols; D003684:Dehydrocholesterols; D005609:Free Radicals; D000072376:Oxysterols; D013261:Sterols; C026359:cholesta-5,8-dien-3 beta-ol; C016705:7-dehydrocholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase
keywords: 7-Dehydrocholesterol; 7-Dehydrocholesterol reductase; 8-Dehydrocholesterol; Liquid chromatography–; Oxysterol; Sterol; mass spectrometry