title: Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with severe vitamin D deficiency.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  We conclude that CYP2R1 is a major vitamin D 25-hydroxylase that plays a fundamental role in activation of this essential vitamin.
authors.affiliation: Department of Pediatrics, Endocrinology Division, King Abdulaziz Medical City-Riyadh, College of Medicine, King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh 11155, Kingdom of Saudi Arabia. almutair.angham@gmail.com
authors.forename: Angham N
authors.initials: AN
authors.lastname: Al Mutair
authors.forename: Ghada H
authors.initials: GH
authors.lastname: Nasrat
authors.forename: David W
authors.initials: DW
authors.lastname: Russell
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D002112:Calcifediol / Q000097:blood; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics* / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D012529:Saudi Arabia; D012720:Severity of Illness Index; D014808:Vitamin D Deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol