title: Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes.
abstract: Since 1998, five disorders involving enzyme defects in post-squalene cholesterol biosynthesis have been identified-desmosterolosis, X-linked dominant chondrodysplasia punctata, CHILD syndrome, lathosterolosis, and hydrops-ectopic calcification-moth-eaten skeletal dysplasia. They join the most common cholesterol biosynthetic disorder, Smith-Lemli-Opitz syndrome, whose underlying defect was identified in 1993. All are associated with major developmental malformations that are unusual for metabolic disorders. The existence of mouse models for five of these disorders is beginning to enable more detailed developmental and in vitro studies examining the mechanisms involved in disease pathogenesis. In this review, an overview of the cholesterol biosynthetic pathway will be presented. Clinical features of the human disorders and mouse models of post-squalene cholesterol biosynthesis will then be discussed.
authors.affiliation: Center for Molecular and Human Genetics, Columbus Children's Research Institute and Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA. hermang@pediatrics.ohio-state.edu
authors.forename: Gail E
authors.initials: GE
authors.lastname: Herman
mesh_terms: D000818:Animals; D001848:Bone Diseases, Developmental / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D002806:Chondrodysplasia Punctata / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D008659:Metabolic Diseases / Q000235:genetics* / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics
chemical_list: C001521:lathosterol; D002784:Cholesterol