Disease relevance of Smith-Lemli-Opitz Syndrome

• Clinical overlap with lethal acrodysgenital dwarfism (Smith-Lemli-Opitz syndrome type II) and hydrolethalus syndrome is discussed [1].
• The Smith-Lemli-Opitz syndrome (SLOS) is a congenital birth defect syndrome caused by a deficiency of 3beta-hydroxysterol Delta(7)-reductase, the final enzyme in the cholesterol biosynthetic pathway [2].
• Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: does abnormal cholesterol metabolism affect the function of Sonic Hedgehog [3]?
• We describe three unrelated patients with adrenal insufficiency and RSH or Smith-Lemli-Opitz syndrome (SLOS), a disorder due to deficient synthesis of cholesterol [4].
• This report describes the first case of a fatal disseminated adenovirus type 7 infection in a child with Smith-Lemli-Opitz syndrome, a rare autosomal recessive disorder due to a primary enzymatic defect in cholesterol metabolism [5].

Psychiatry related information on Smith-Lemli-Opitz Syndrome

• The Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a deficiency of the enzyme 7-dehydrocholesterol Delta(7)-reductase [6].

High impact information on Smith-Lemli-Opitz Syndrome

• Smith-Lemli-Opitz syndrome (SLOS), desmosterolosis and lathosterolosis are human syndromes caused by defects in the final stages of cholesterol biosynthesis [7].
• Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome [8].
• 7-Dehydrocholesterol-dependent proteolysis of HMG-CoA reductase suppresses sterol biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH syndrome [9].
• Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene [10].
• Their molecular target is the Delta7-sterol reductase (EC 1.3.1.21), suspected to be defective in the Smith-Lemli-Opitz syndrome, a frequent inborn disorder of sterol metabolism [11].

Chemical compound and disease context of Smith-Lemli-Opitz Syndrome

• Smith-Lemli-Opitz syndrome (SLOS) is a genetic syndrome caused by mutations in the 3beta-hydroxysterol Delta(7)-reductase gene (DHCR7) [12].
• Development and characterization of a hypomorphic Smith-Lemli-Opitz syndrome mouse model and efficacy of simvastatin therapy [12].
• The Smith-Lemli-Opitz syndrome is a disorder of morphogenesis resulting from an enzymatic defect in the last step of cholesterol metabolism (reduction of 7-dehydrocholesterol) [13].
• Identification of 8-dehydrocholesterol (cholesta-5,8-dien-3 beta-ol) in patients with Smith-Lemli-Opitz syndrome [14].
• The MDMAES derivative was used to develop a rapid screening procedure for the biochemical diagnosis of Smith-Lemli-Opitz syndrome (SLOS) by measuring the dehydrocholesterol/cholesterol ratio in plasma (5 microl) and plasma spotted onto filter paper [15].

Biological context of Smith-Lemli-Opitz Syndrome

• This includes limb malformations that are observed at high frequency in some disorders, such as the Smith-Lemli-Opitz syndrome, indicating a pivotal role of cholesterol in limb morphogenesis [16].
• Molecular genetics of the Smith-Lemli-Opitz syndrome and postsqualene sterol metabolism [13].
• Defective conversion of 7-dehydrocholesterol to cholesterol in cultured skin fibroblasts from Smith-Lemli-Opitz syndrome homozygotes [17].
• Intestinal absorption of cholesterol by patients with Smith-Lemli-Opitz syndrome [18].
• First trimester prenatal diagnosis of Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency) [19].

Anatomical context of Smith-Lemli-Opitz Syndrome

• The ability to manipulate the mass of maternal cholesterol that crosses to the fetus could result in a dramatic improvement in the development of fetuses that lack the ability to synthesize cholesterol, such as those with Smith-Lemli-Opitz syndrome [20].
• Measurement of 3 beta-hydroxysteroid delta 7-reductase activity in cultured skin fibroblasts utilizing ergosterol as a substrate: a new method for the diagnosis of the Smith-Lemli-Opitz syndrome [21].
• Quantification of 7-dehydrocholesterol in plasma and amniotic fluid by liquid chromatography/particle beam-mass spectrometry as a biochemical diagnostic marker for the Smith-Lemli-Opitz syndrome [22].
• The Smith-Lemli-Opitz syndrome is a genetic disorder characterized by typical clinical features including reduced myelination of both brain and peripheral nervous system and defective cholesterol biosynthesis [23].

Gene context of Smith-Lemli-Opitz Syndrome

• Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations [24].
• There was no association of Smith-Lemli-Opitz syndrome severity with LDLR gene variation [25].
• Neonatal mice lacking functional dehydrocholesterol Delta7-reductase (Dhcr7), a model for the human disease of Smith-Lemli-Opitz syndrome, die within 24 hours of birth [26].
• The cDNA encoding the 471-amino acid rat 7-dehydrocholesterol reductase (DHCR), an enzyme that has been implicated in both cholesterol biosynthesis and developmental abnormalities (e.g. Smith-Lemli-Opitz syndrome) in mammals, has been cloned and sequenced, and the primary structure of the enzyme has been deduced [27].
• We have investigated whether apolipoprotein E, a major component of the cholesterol transport system in human beings, is a modifier of the clinical severity of Smith-Lemli-Opitz syndrome [25].

Analytical, diagnostic and therapeutic context of Smith-Lemli-Opitz Syndrome

• The qualitative and quantitative determination of cholesterol and 7-dehydrocholesterol (7-DHC) in plasma as a biochemical diagnostic marker for the Smith-Lemli-Opitz syndrome by liquid chromatography/particle beam interface-mass spectrometry (LC/PB-MS) is presented [22].
• The discovery of the biochemical defect causing Smith-Lemli-Opitz syndrome has resulted in the development of a diagnostic test and a potentially beneficial treatment (dietary cholesterol supplementation) [28].
• A method is described for quantification of 7-dehydrocholesterol (7DHC) and other neutral sterols by gas chromatography/mass spectrometry for diagnosis of Smith-Lemli-Opitz syndrome, an apparent primary defect of cholesterol biosynthesis associated with low plasma levels of cholesterol and high levels of its precursor, 7DHC [29].
• Recognition of Smith-Lemli-Opitz syndrome (RSH) in the fetus: utility of ultrasonography and biochemical analysis in pregnancies with low maternal serum estriol [30].

References