The Smith Lemli Opitz (SLOS) syndrome is a genetic syndrome in man associated with mental retardation and birth defects, and due to a defect in cholesterol synthesis. Affected individuals have low cholesterol levels and elevated levels of cholesterol percursors. SLOS is a natural model of cholesterol synthetic defects, and understanding this condition at the biochemical and molecular level will advance our knowledge of cholesterol metabolism in general. We carry out clinical and translational research relating to disorders of cholesterol synthesis.  Our research subjects are admitted to the clinical research center and metabolic studies are performed.  In addition to clinical studies, we are also pursuing in vitro studies. Together with our collaborators at the NIH, we (along with 2 other groups simultaneously) identified mutations in the 7-dehydrocholesterol delta 7 reductase gene as the cause of SLOS. We are currently involved in identification of mutations in the gene in a number of patients. These studies will allow determination of genotype /  phenotype correlations in SLOS. In addition, sterol synthesis in cultured fibroblasts of SLOS patients is measured. With this in vitro model, possible treatment modalities such as the use of HMG CoA reductase inhibitors can be studied in cell culture prior to their application in patients. Finally, our newest research area is devoted to getting cholesterol into the brain.  We plan both animal and human studies in that regard.  In summary, our lab focuses on elucidation ofthe molecular and biochemical basis of cholesterol synthesis disorders and novel approaches to their treatment.

Sikora DM, Pettit-Kekel K, Penfield J, Merkens L, Steiner RD, The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome.  Am J Med Genet A. 140A:1511-1518, 2006.

Pappu AS, Connor WE, Merkens LM, Jordan JM, Penfield JA, Illingworth DR, Steiner RD, Increased non-sterol isoprenoids, dolichol and ubiquionone in the Smith-Lemli-Opitz Syndrome: effects of dietary cholesterol. J. Lipid Res. 47:2789-2798, 2006.

DeBarber AE, Lütjohann D,  Merkens L, Steiner RD.  Liquid chromatography-tandem mass spectrometry determination of plasma 24S-hydroxycholesterol with chromatographic separation of 25-hydroxycholesterol.  Anal Biochem.  381:151-3, 2008.   PMID: 18555788

Merkens LS, Jordan JM, Penfield JA, Lütjohann D, Connor WE, Steiner RD.   Plasma Plant Sterol Levels Do Not Reflect Cholesterol Absorption in Children with Smith-Lemli-Opitz Syndrome.  J Pediatr 2008 Dec 20. [Epub ahead of print] PMID: 19101685

Chan Y-M, Merkens LS, Connor WE, Roullet J-B, Penfield JA, Jordan JM, Steiner RD, Jones PJH.  Effects of dietary cholesterol and simvastatin on cholesterol synthesis in Smith-Lemli-Opitz syndrome (SLOS).  Ped Res  (In Press)

Merkens LS, Wassif C, Healy K,  Pappu AS,  DeBarber AE, Penfield JA, Lindsay RA, Roullet J-B, Porter  FD, Steiner RD.  Smith-Lemli-Opitz Syndrome and Inborn Errors of Cholesterol Synthesis: Summary of the 2007 SLO/RSH Foundation Scientific Conference Sponsored by the National Institutes of Health.  Genetics in Medicine (In Press)

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