Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients
Smith-Lemli-Opitz syndrome (SLOS) is caused by mutations in the gene encoding 3β-hydroxysterol-Δ7-reductase and as a result of this defect, 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC) accumulate in the fluids and tissues of patients with this syndrome. Both 7- and 8-DHC are suscept...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2013
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| In: |
Journal of lipid research
Year: 2021, Volume: 54, Issue: 1, Pages: 244-253 |
| ISSN: | 1539-7262 |
| DOI: | 10.1194/jlr.M031732 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1194/jlr.M031732 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022227520417791 
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| Author Notes: | Wei Liu, Libin Xu, Connor R. Lamberson, Louise S. Merkens, Robert D. Steiner, Ellen R. Elias, Dorothea Haas, and Ned A. Porter |
| Summary: | Smith-Lemli-Opitz syndrome (SLOS) is caused by mutations in the gene encoding 3β-hydroxysterol-Δ7-reductase and as a result of this defect, 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC) accumulate in the fluids and tissues of patients with this syndrome. Both 7- and 8-DHC are susceptible to peroxidation reactions, and several biologically active DHC oxysterols are found in cell and animal models of SLOS. Ex vivo oxidation of DHCs can be a confounding factor in the analysis of these sterols and their esters, and we developed HPLC/MS methods that permit the direct analysis of cholesterol, 7-DHC, 8-DHC, and their esters in human plasma, thus avoiding ex vivo oxidation. In addition, three oxysterols were classified as endogenously formed products by the use of an isotopically-labeled 7-DHC (d7-7-DHC) added to the sample before workup, followed by MS analysis of products formed. Analysis of 17 SLOS plasma samples shows that 8-DHC linoleate correlates better with the SLOS severity score of the patients than other sterols or metabolites, including cholesterol and 7-DHC. Levels of 7-ketocholesterol also correlate with the SLOS severity score. 8-DHC esters should have utility as surrogate markers of severity in SLOS for prognostication and as endpoints in clinical trials. |
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| Item Description: | Available online 4 January 2021 Published, JLR Papers in Press, October 16, 2012 Gesehen am 19.05.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1539-7262 |
| DOI: | 10.1194/jlr.M031732 |