[The role of cholesterol in embryogenesis and the Smith-Lemli-Opitzov syndrom].

Abstract

The role of cholesterol in cell biology has been known for years. The sight of cholesteol biological function has changed after the discovery that the genetic disorder Smith-Lemli-Opitz syndrome is caused by a defect in cholesterol biosynthetic pathway. Cholesterol has an important role in regulation and modification of Hedgehog proteins, what links cholesterol to early embryonic development. Hedgehog proteins comprise a family of secreted signaling molecules that are essential for embryonic patterning and morphogenesis. The deficit of cholesterol during embryogenesis causes severe abnormalities in SLOS because of disrupt autoprocessing of hedgehog proteins. SLOS is an autosomal recessive disorder of sterol metabolism. The underlying pathogenetic basis for SLOS has been shown to be a deficiency of 7-dehydrocholesterol reductase, which catalyzes the last step in cholesterol biosynthesis. Reduced enzyme activity leads to a deficit of cholesterol and accumulation of precursor sterols. The human 7-dehydrocholesterol reductase gene (DHCR7) is localized on chromosome 11q 12-13.