Genetic defects in postsqualene cholesterol biosynthesis

Trends Endocrinol Metab. 2000 Apr;11(3):106-14. doi: 10.1016/s1043-2760(00)00235-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cholesterol / biosynthesis*
  • Chondrodysplasia Punctata / genetics
  • Chondrodysplasia Punctata / metabolism
  • Desmosterol / metabolism
  • Genes, Dominant
  • Humans
  • Metabolism, Inborn Errors / genetics*
  • Mice
  • Mice, Mutant Strains / genetics
  • Mice, Mutant Strains / metabolism
  • Smith-Lemli-Opitz Syndrome / genetics
  • Smith-Lemli-Opitz Syndrome / metabolism
  • Squalene / metabolism*
  • Sterols / biosynthesis
  • X Chromosome


  • Sterols
  • Desmosterol
  • Squalene
  • Cholesterol