The Smith-Lemli-Opitz syndrome (SLOS) is one of the archetypical multiple .. and regulation of cholesterol uptake as well as de novo cholesterol synthesis will. Le syndrome de Smith-Lemli-Opitz (SLO) est un syndrome polymalformatif grave, de transmission autosomique récessive, lié à un déficit en. Smith-Lemli-Opitz syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by distinctive facial features, small.


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For example, cholesterol is necessary for the ligand binding activity of the serotonin receptor. Cholesterol modulates the properties of the membrane such as membrane curvatureand may regulate the fusion of vesicles with the cell membrane.

It may also facilitate the recruitment of complexes necessary for exocytosis. Given that neurons rely heavily on exocytosis for the transmission of impulsescholesterol is a very important part of the nervous system.

Syndrome de smith lemli opitz particularly relevant pathway in which cholesterol takes place is the Hedgehog signaling pathway.

Smith–Lemli–Opitz syndrome

This pathway is very important during embryonic developmentand involved in deciding the fate of cells i. Hedgehog proteins are also involved in the transcription of genes that regulate cell proliferation and differentiation.

  • Orphanet: Smith Lemli Opitz syndrome
  • Smith-Lemli-Opitz Syndrome - GeneReviews® - NCBI Bookshelf
  • Smith-Lemli-Opitz syndrome

Cholesterol is important to this pathway because it undergoes covalent bonding to Hedgehog proteins, resulting in their activation. Without cholesterol, the signaling activity is disrupted and cell differentiation may be impaired.

These include bile acids important in processing dietary fatsoxysterolsneurosteroids involved in neurotransmission and excitationglucocorticoids involved in immune and inflammatory processesmineralocorticoids osmotic balanceand sex steroids i.

Myelination occurs most rapidly during prenatal development, meaning that syndrome de smith lemli opitz demand for cholesterol biosynthesis is very high. The structure of the DHCR7 rat gene is very similar to the structure of the human gene.

Smith–Lemli–Opitz syndrome - Wikipedia

There is also evidence that its activity may be regulated by tissue specific transcription, and alternative splicing. As outlined above, syndrome de smith lemli opitz enzyme DHCR7 catalyzes the reduction of 7DHC to cholesterol, as well as the reduction of 7-dehydrodesmosterol to desmosterol.

It is also thought to contain iron.

The human syndrome de smith lemli opitz of this enzyme is predicted to have a molecular weight of 54, kDaand an isoelectric point of 9. It contains multiple sterol reductase motifs, as would be expected given its function. It contains a potential sterol-sensing domain SSDwhose function is unknown but thought to be necessary for binding sterol substrates.

It also syndrome de smith lemli opitz multiple sites of phosphorylation, including potential protein kinase C and tyrosine kinase sites regulatory enzymes responsible for phosphorylation.

The exact function of phosphorylating DHCR7 is yet unknown, but it is thought to be involved in the regulation of its activity.


These typically reduce the function of the enzyme but may not inhibit it completely. Much depends on the nature of the mutation i. Null mutations are much less common, these mutations produce either a completely dysfunctional enzyme, or no enzyme at all.

This disrupts the joining of exons eight and nine, and results in the insertion of nucleotides into the DHCR7 transcript.

This is a nonsense mutation, thus patients that are homozygous for this allele are severely affected.

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It syndrome de smith lemli opitz thought that this mutation first occurred in the British Islesand it has a carrier those that are heterozygous for the allele but not affected frequency of 1.

The frequency of mutations differs for various ethnicities, depending on the origin of the mutation.


It is a missense mutation and tends to be associated with less severe symptoms. This mutation is the most common one seen in patients of Italian, Cuban, and Mediterranean descent.

Smith Lemli Opitz Syndrome - NORD (National Organization for Rare Disorders)

This nonsense mutation causes protein termination, such that the enzyme DHCR7 would not be formed. It is thought to have arisen in Southern Poland and is most common in Northern Europe. For example, the sterol reductase motifs are common sites of mutation.