Molecular genetics of vitamin D- dependent hereditary rickets

Horm Res. 2002;57(3-4):73-8. doi: 10.1159/000057955.


Vitamin D exerts a wide variety of biological actions. The active form of vitamin D, 1alpha,25(OH)(2)D(3), is biosynthesized from cholesterol. The final, critical step in this biosynthesis is conversion from 25-hydroxyvitamin D(3) to 1alpha,25(OH)(2)D(3) by the enzyme 25-hydroxyvitamin D(3) 1alpha-hydroxylase(CYP27B1)[1alpha(OH)ase]. 1alpha,25(OH)(2)D(3) transcriptionally controls the expression of a particular set of target genes mediated through nuclear vitamin D receptor(VDR) acting as a ligand-inducible factor. Two types of vitamin D-dependent hereditary rickets (VDDR) are known to be caused by mutations in the 1alpha(OH)ase and VDR genes. The 1alpha(OH)ase gene is responsible for VDDR type I, and VDR for type II. Both of the diseases display an autosomal-recessive trait, but clinical features and response to administrated 1alpha,25(OH)(2)D(3) are distinct. The phenotypes of the gene KO mice deficient of 1alpha(OH)ase and VDR exhibited the clinical abnormalities observed in the VDDR patients.

Publication types

  • Review

MeSH terms

  • Calcitriol / biosynthesis
  • Humans
  • Hydroxycholecalciferols / metabolism
  • Hypophosphatemia, Familial / genetics*
  • Mutation
  • Vitamin D / biosynthesis*


  • Hydroxycholecalciferols
  • Vitamin D
  • Calcitriol