Disorders of Cholesterol Biosynthesis, Genetics of

Carrie A Phillipi, Oregon Health & Science University, Portland, Oregon, USA
Robert D Steiner, Oregon Health & Science University, Portland, Oregon, USA

Published online: May 2008

DOI: 10.1002/9780470015902.a0020223

Smith-Lemli-Opitz syndrome (SLOS) is the most common and best understood of the inborn errors of cholesterol metabolism. Comprising a heterogeneous group of disorders, inborn errors in cholesterol biosynthesis result in characteristic but variable phenotypes. SLOS is an inherited disorder caused by mutations in DHCR7 which encodes the final enzyme in the cholesterol synthetic pathway. The features of SLOS are thought to be related to cholesterol deficiency and/or accumulation of cholesterol precursors and their metabolites. Therefore, supplementation of cholesterol is a commonly employed potential therapy. A better understanding of SLOS and other inborn errors of cholesterol biosynthesis may shed light on the importance of cholesterol biosynthesis in embryo- and morphogenesis and provide clues to treatment.

Keywords: Smith-Lemli-Opitz syndrome; inborn error of metabolism; sterol; cholesterol; cholesterol biosynthesis

Figure 1. Cholesterol synthesis pathway and human malformation syndromes. The sterol ring structure and carbon position numbering are shown at the top of the figure. Human malformation syndromes are in boldface type. Cholesterol is synthesized from squalene in a series of enzymatic reactions denoted by numbers: 1, squalene monooxygenase and squalene cyclase; 2, lanosterol 14--demethylase; 3, 3-hydroxysterol 14-reductase; 4, C4 demethylation complex (C4-sterol methyloxidase C4-sterol decarboxylase [NSDHL], and 3-ketoreductase); 5, 3-hydroxysterol 8, 7-isomerase; 6, lathosterol 5-desaturase; 7, 3-hydroxysterol 7-reductase; 8, 3-hydroxysterol 24-reductase. Reproduced with permission from Porter FD (2002).
Figure 2. Typical phenotypic facial features of children with SLOS include microcephaly, small low-set ears, a broad high forehead, blepharoptosis, epicanthal folds, a broad nasal bridge, a short nose with anteverted nares, cleft palate and micrognathia. Images supplied by Oregon Health and Science University.
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    Yu H and Patel SB (2005) Recent insights into the Smith-Lemli-Opitz syndrome. Clinical Genetics 68(5): 383–391. Review. Erratum in: Clinical Genetics. 68(6):570. PMID: 16207203 [PubMed - indexed for MEDLINE].

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Molecular Genetics of Common and Complex Disease | Specific Genetic Disorders | Enzymes: Structure and Action Mechanism | Lipids: Structure, Function, Metabolism
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Article Title: Disorders of Cholesterol Biosynthesis, Genetics of
 
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Phillipi, Carrie A, and Steiner, Robert D(May 2008) Disorders of Cholesterol Biosynthesis, Genetics of. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020223]