DHCR7 mutations causing the Smith-Lemli-Opitz syndrome

The Smith-Lemli-Opitz Syndrome (SLOS) is a metabolic malformation and mental retardation syndrome that is casued by a defect in cholesterol biosynthesis. The resulting loss of cholesterol leads to a spectrum from mild to very severe phenotype. The DHCR7 gene encodes Delta 7 sterol reductase, the enzyme catalyzing the reduction of 7-dehydrocholesterol to cholesterol. This review provides an overview of knowledge about mutations leading to SLOS. It describes why and how age and origin of mutations are estimated. It demonstrates that mutational spectra are population specific and that so-called null mutations have a high carrier frequency, probably not due to selection alone. Finally, a correlation between DHCR7 genotype and SLOS phenotype and a genetic modifying factor for this disease is described.