DHCR7 mutations causing the Smith—Lemli—Opitz syndrome

Abstract

The Smith—Lemli—Opitz Syndrome (SLOS) is a metabolic malformation and mentalretardation syndrome that is casued by a defect in cholesterol biosynthesis. The resultingloss of cholesterol leads to a spectrum from mild to very severe phenotype. The DHCR7 geneencodes Ä7 sterol reductase, the enzyme catalyzing the reduction of 7-dehydrocholesterolto cholesterol. This review provides an overview of knowledge about mutations leading toSLOS. It describes why and how age and origin of mutations are estimated. It demonstratesthat mutational spectra are population specific and that so-called null mutations have ahigh carrier frequency, probably not due to selection alone. Finally, a correlation betweenDHCR7 genotype and SLOS phenotype and a genetic modifying factor for this diseaseis described.

Keywords:

• Cholesterol
• Ä7 sterol reductase
• DHCR7