title: Lack of mutations in CYP2D6 and CYP27 in patients with apparent deficiency of vitamin D 25-hydroxylase.
abstract: Activation of vitamin D requires hepatic 25-hydroxylation and renal 1alpha-hydroxylation. Defects in renal P450c1alpha are well-described, but few patients with defective vitamin D 25-hydroxylation are reported. The cytochrome P450 enzymes CYP2D6 and CYP27 are potential 25-hydroxylases. We sequenced both genes in two reported families with hepatic 25-hydroxylase deficiency and found no mutations. 25-Hydroxylation occurs in both mitochondria and microsomes. The existence genes encoding distinct enzymes would provide genetic redundancy, explaining the rarity of apparent vitamin D 25-hydroxylase deficiency.
authors.affiliation: Department of Pediatrics, University of California, San Francisco, CA 94143-0978, USA.
authors.forename: Chin Jia
authors.initials: CJ
authors.lastname: Lin
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.forename: Sujeewa D
authors.initials: SD
authors.lastname: Wijesuriya
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdullah
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Casella
authors.forename: Walter L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency*; D053493:Cholestanetriol 26-Monooxygenase; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D006801:Humans; D008664:Metal Metabolism, Inborn Errors / Q000235:genetics*; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D013250:Steroid Hydroxylases; D019389:Cytochrome P-450 CYP2D6; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase