in an enzyme involved in cholesterol synthesis, the resulting biochemical characteristics may be predictable. Most patients have lowered plasma cholesterol levels (hypocholesterolemia). However, approximately 10% may show normal cholesterol levels, and decreased concentrations of cholesterol are not solely indicative of SLOS. Increased levels of cholesterol precursors are also common in SLOS. In particular, elevated levels of 7-dehydrocholesterol are fairly specific to SLOS. Genetics DHCR7 The gene encoding DHCR7 (labeled as DHCR7) was cloned in 1998, and has been mapped to chromosome 11q12-13. It is 14100 base pairs of DNA in length, and contains nine exons, the corresponding mRNA is 2786 base pairs in length (the remaining DNA sequence is intronic). The structure of the DHCR7 rat gene is very similar to the structure of the human gene. The highest levels of DHCR7 expression have been detected in the adrenal gland, the testis, the liver and in brain tissue. Its expression is induced by decreased sterol concentrations via sterol regulatory binding proteins (SREBP). There is also evidence that its activity may be regulated by tissue specific transcription, and alternative splicing. As outlined above, the enzyme DHCR7 catalyzes the reduction of 7DHC to cholesterol, as well as the reduction of 7-dehydrodesmosterol to desmosterol. It requires NADPH as a cofactor for this reduction, and may involve the activity of cytochrome-P450 oxidoreductase. It is also thought to contain iron. DHCR7 is an integral membrane protein of the endoplasmic reticulum, and computer models have predicted up to nine transmembrane domains. DHCR7 is most efficient at reducing 7DHC, but it is known to reduce the carbon 7 double bond of other sterols, indicating a range of substrate specificity. The human version of this enzyme is predicted to have a molecular weight of 54,489 kDa, and an isoelectric point of 9.05. The amino acid sequence that encodes DHCR7 is predicted to contain 475 amino acids, as well as several protein motifs. It contains multiple sterol reductase motifs, as would be expected given its function. It contains a potential sterol-sensing domain (SSD), whose function is unknown but thought to be necessary for binding sterol substrates. It also includes multiple sites of phosphorylation, including potential protein kinase C and tyrosine kinase sites (regulatory enzymes responsible for phosphorylation). The exact function of phosphorylating DHCR7 is yet unknown, but it is thought to be involved in the regulation of its activity. Mutations and incidence SLOS is an autosomal recessive disorder. More