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.  In Press, AJMG, 2006.

Tulenko TN, Boeze-Battaglia K, Preston Mason R, Tint GS, Steiner RD, Connor WE, Labelle EF, William E. Connor, Labelle EF.  A membrane defect in the pathogenesis of the Smith-Lemli-Opitz Syndrome.  J Lipid Res.;47:134-43, 2006.

Wassif CA, Zhu P, Kratz L, Krakowiak PA, Battaile KP, Weight FF, Grinberg A, Steiner RD, Nwokoro NA, Kelley RI, Stewart RR, Porter FD (2001). Biochemical, phenotypic and neurophysiological characterization of a genetic mouse model of RSH / Smith--Lemli--Opitz syndrome. Hum Mol Genet10(6):555-64.

Steiner RD, Linck LM, Flavell DP, Lin DS, Connor WE (2000). Sterol balance in the Smith-Lemli-Opitz syndrome. Reduction in whole body cholesterol synthesis and normal bile acid production. J Lipid Res41(9):1437-47.

Wassif CA, Maslen C, Kachilele-Linjewile S, Lin D, Linck LM, Connor WE, Steiner RD, Porter FD (1998). Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome. Am J Hum Genet63(1):55-62.

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