Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with severe vitamin D deficiency

J Clin Endocrinol Metab. 2012 Oct;97(10):E2022-5. doi: 10.1210/jc.2012-1340. Epub 2012 Aug 1.


Context: Inherited forms of vitamin D deficiency are rare causes of rickets and to date have been traced to mutations in three genes, VDR, encoding the 1α,25-dihydroxyvitamin D receptor, CYP27B1, encoding the vitamin D 1α-hydroxylase, and CYP2R1, encoding a microsomal vitamin D 25-hydroxylase.

Results: Multiple mutations have been identified in VDR and CYP27B1 in patients with rickets, and thus, the roles of these two genes in vitamin D metabolism are unassailable. The case is less clear for CYP2R1, in which only a single mutation, L99P in exon 2 of the gene, has been identified in Nigerian families, and because multiple enzymes with vitamin D 25-hydroxylase activity have been identified. Here we report molecular genetic studies on two siblings from a Saudi family who presented with classic symptoms of vitamin D deficiency. The affected offspring inherited two different CYP2R1 mutations (367+1, G→A; 768, iT), which are predicted to specify null alleles.

Conclusion: We conclude that CYP2R1 is a major vitamin D 25-hydroxylase that plays a fundamental role in activation of this essential vitamin.

Publication types

  • Case Reports

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Adolescent
  • Calcifediol / blood
  • Cholestanetriol 26-Monooxygenase / genetics*
  • Cholestanetriol 26-Monooxygenase / metabolism
  • Cytochrome P450 Family 2
  • Family Health
  • Female
  • Humans
  • Male
  • Pedigree
  • Point Mutation / genetics*
  • Saudi Arabia
  • Severity of Illness Index*
  • Vitamin D Deficiency / genetics*
  • Vitamin D Deficiency / metabolism


  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcifediol