desmosterol and Smith-Lemli-Opitz-Syndrome
desmosterol has been researched along with Smith-Lemli-Opitz-Syndrome* in 7 studies
Reviews
3 review(s) available for desmosterol and Smith-Lemli-Opitz-Syndrome
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Genetic defects in postsqualene cholesterol biosynthesis.
In humans and mice, four different genetic defects in the nine biosynthetic steps from lanosterol to cholesterol have been identified. They impair the activity of a putative C3-sterol dehydrogenase (Nshdl, X-linked dominant bare patches/striated mutation in mice), the sterol delta 8-delta 7 isomerase/EBP (Ebp, X-linked dominant tattered mutation in mice; chondrodysplasia punctata (CDPX2) in humans), the delta 24-sterol reductase (autosomal recessive desmosterolosis) and the delta 7-sterol reductase (DHCR7 gene, autosomal recessive Smith-Lemli-Opitz syndrome in humans). These inborn errors in postsqualene cholesterol metabolism result in dysmorphogenetic syndromes of variable severity. The X-linked dominant mutations result in mosaicism in females, as a result of X-inactivation, and midgestational lethality in males. The mechanisms by which the depletion of cholesterol or the accumulation of intermediates impair morphogenetic programs are unclear. So far, no cellular processes that require an intact cholesterol biosynthetic pathway have been identified, although the morphogenetic hedgehog-patched signaling cascade is a candidate. Topics: Animals; Cholesterol; Chondrodysplasia Punctata; Desmosterol; Genes, Dominant; Humans; Metabolism, Inborn Errors; Mice; Mice, Mutant Strains; Smith-Lemli-Opitz Syndrome; Squalene; Sterols; X Chromosome | 2000 |
Inborn errors of cholesterol biosynthesis.
Disorders of cholesterol biosynthesis have recently emerged as important errors of metabolism that collectively have taught us many new genetic and biochemical lessons. Whereas most metabolic diseases are characterized by exclusively or largely postnatal biochemical toxicities or deficiencies, disorders of cholesterol biosynthesis are notable for their severe effects on prenatal development. The remarkable embryonic consequences of abnormal cholesterol biosynthesis are exemplified by Smith-Lemli-Opitz syndrome (SLOS), a well-known multiple congenital anomaly syndrome only recently discovered to be caused by a deficiency in the last step in cholesterol biosynthesis. Equally surprising has been the discovery that primary defects of cholesterol biosynthesis cause several different forms of congenital skeletal dysplasia, most notably X-linked dominant chondrodysplasia punctata, or Conradi-Hünermann syndrome. Yet another sterol disorder, desmosterolosis, caused by defective activity of desmosterol reductase, combines a severe osteosclerotic skeletal dysplasia with multiple embryonic malformations similar to those of SLOS. The discovery of the biochemical basis of these diverse genetic disorders has provided not only accurate biochemical methods for their diagnosis and prenatal diagnosis, but also new insights into the biochemistry of vertebrate embryonic development. Among the lessons we have learned from the study of inborn errors of cholesterol biosynthesis, one of the most important is that the abnormal cholesterol metabolism of SLOS impairs the function of "Sonic hedgehog" and other related embryonic "signaling proteins" that help determine the vertebrate body plan during the earliest weeks of embryonic development. Most significant clinically has been the realization that many of the postnatal clinical problems of patients with SLOS are direct consequences of the inability to synthesize the large amounts of cholesterol needed for growth and for the synthesis of compounds derived from cholesterol, such as steroid hormones. In addition to the important finding that supplementary cholesterol eliminates or ameliorates many of the feeding and growth problems of SLOS, the discovery that the autistic behaviors of children with SLOS can be reduced or even eliminated by treatment with supplementary dietary cholesterol has been one of the most startling. Moreover, clinical and basic research on prenatal cholesterol nutrition in SLOS and various animal model systems Topics: Autistic Disorder; Bone Diseases, Developmental; Child; Cholesterol; Cholesterol, Dietary; Chondrodysplasia Punctata; Desmosterol; Diagnosis, Differential; Humans; Lipid Metabolism, Inborn Errors; Mevalonic Acid; Smith-Lemli-Opitz Syndrome; Steroids | 2000 |
Disorders of cholesterol biosynthesis.
Topics: Anticholesteremic Agents; Cholesterol; Desmosterol; Disease Models, Animal; Humans; Infant, Newborn; Lanosterol; Metabolism, Inborn Errors; Smith-Lemli-Opitz Syndrome; trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride | 1998 |
Other Studies
4 other study(ies) available for desmosterol and Smith-Lemli-Opitz-Syndrome
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Desmosterolosis and desmosterol homeostasis in the developing mouse brain.
Topics: Abnormalities, Multiple; Animals; Brain; Cell Membrane; Cholesterol; Dehydrocholesterols; Desmosterol; Female; Homeostasis; Lipid Metabolism, Inborn Errors; Male; Mice; Mutation; Nerve Tissue Proteins; Neurons; Oxidoreductases Acting on CH-CH Group Donors; Smith-Lemli-Opitz Syndrome; Sterols; Tandem Mass Spectrometry | 2019 |
Analysis by liquid chromatography-mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7(Δ3-5/T93M) mouse: a model of Smith-Lemli-Opitz syndrome.
In this study the sterol and oxysterol profile of newborn brain from the Dhcr7(Δ3-5/T93M) mouse model of Smith-Lemli-Opitz syndrome (SLOS) has been investigated. This is a viable mouse model which is compound heterozygous containing one null allele and one T93M mutation on Dhcr7. We find the SLOS mouse has reduced levels of cholesterol and desmosterol and increased levels of 7- and 8-dehydrocholesterol and of 7- and 8-dehydrodesmosterol in brain compared to the wild type. The profile of enzymatically formed oxysterols in the SLOS mouse resembles that in the wild type but the level of 24S-hydroxycholesterol, the dominating cholesterol metabolite, is reduced in a similar proportion to that of cholesterol. A number of oxysterols abundant in the SLOS mouse are probably derived from 7-dehydrocholesterol, however, the mechanism of their formation is unclear. Topics: Animals; Animals, Newborn; Cholesterol; Chromatography, Liquid; Desmosterol; Gene Knock-In Techniques; Mice; Mice, Mutant Strains; Oxidation-Reduction; Oxidoreductases Acting on CH-CH Group Donors; Smith-Lemli-Opitz Syndrome; Spectrometry, Mass, Electrospray Ionization; Sterols | 2013 |
Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome.
Our recent studies have focused on cholesterol synthesis in mouse models for 7-dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz syndrome. Investigations of such mutants have relied on tissue and blood levels of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we have identified and quantified cholesterol and its precursors (7DHC, desmosterol, lathosterol, lanosterol and cholest-7,24-dien-3β-ol) in mouse hair. The components were characterized and their concentrations were compared to those found in mouse skin and serum. Hair appeared unique in that desmosterol was a major sterol component, almost matching in concentration cholesterol itself. In DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Δ(7) sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C ratio in hair was typically about sevenfold the value in serum or skin and the DHD/D ratio was 100× that of the serum 7DHC/C ratio. Mutant mice compensate for their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become close to normal. That hair retains high relative concentrations of the dehydro precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is slower to develop at the site of hair cholesterol synthesis. Topics: Animals; Cholesterol; Dehydrocholesterols; Desmosterol; Disease Models, Animal; Gas Chromatography-Mass Spectrometry; Hair; Lanosterol; Mice; Mutation; Oxidoreductases Acting on CH-CH Group Donors; Skin; Smith-Lemli-Opitz Syndrome; Sterols | 2010 |
A comparison of the behavior of cholesterol and selected derivatives in mixed sterol-phospholipid Langmuir monolayers: a fluorescence microscopy study.
Eukaryotic cells require sterols to achieve normal structure and function of their plasma membranes, and deviations from normal sterol composition can perturb these features and compromise cellular and organism viability. The Smith-Lemli-Opitz syndrome (SLOS) is a hereditary metabolic disease involving cholesterol (CHOL) deficiency and abnormal accumulation of the CHOL precursor, 7-dehydrocholesterol (7DHC). In this study, the interactions of CHOL and the related sterols desmosterol (DES) and 7DHC with l-alpha-dipalmitoylphosphatidylcholine (DPPC) monolayers were compared. Pressure-area isotherms and fluorescence microscopy were used to study DPPC monolayers containing 0, 10, 20, or 30 mol% sterol. Similar behavior was noted for CHOL- and DES-containing DPPC monolayers with both techniques. However, while 7DHC gave isotherms similar to those obtained with the other sterols, microscopy indicated limited domain formation with DPPC, indicating that 7DHC packs somewhat differently in DPPC membranes compared to CHOL and DES. These results are discussed in relation to SLOS pathobiology. Topics: 1,2-Dipalmitoylphosphatidylcholine; Cholesterol; Dehydrocholesterols; Desmosterol; Humans; Membranes, Artificial; Microscopy, Fluorescence; Pressure; Smith-Lemli-Opitz Syndrome; Surface Properties | 2005 |