Cholesterol precursors and facial clefting.
Inborn errors of cholesterol synthesis cause human malformation syndromes, including Smith-Lemli-Opitz syndrome, lathosterolosis, desmosterolosis, X-linked dominant chondrodysplasia punctata type 2, and congenital hemidysplasia with ichthyosiform erythroderma and limb defects. Because adequate cholesterol is not transported across the placenta, low cholesterol and elevated sterol precursor levels are present during embryogenesis. It has been debated whether the malformations result from low cholesterol or the buildup of sterol precursors. In this issue of the JCI, Engelking et al. provide evidence that sterol precursor accumulation plays a pivotal role in the genesis of facial malformations (see the related article beginning on page 2356).
Porter
Forbes D
FD
Heritable Disorders Branch, National Institute of Child Health and Human Development, NIH, Department of Health and Human Services, Bethesda, Maryland 20892, USA. fdporter@mail.nih.gov
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis* / Q000172:deficiency; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D053823:Hedgehog Proteins; D006801:Humans; D007223:Infant; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009056:Mouth Abnormalities / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics
D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D002784:Cholesterol