The importance of 25-hydroxyvitamin D3 1 alpha-hydroxylase gene in vitamin D-dependent rickets.

Vitamin D plays a role in a wide variety of biological events such as calcium homeostasis, bone formation and cellular differentiation. An active form of vitamin D acting as a ligand specific vitamin D receptor (VDR), 1 alpha,25(OH)2D3, is biosynthesized from cholesterol, and during this biosynthesis a renal 25-hydroxylation at the final stage by 25-hydroxyvitamin D3 1 alpha-hydroxylase is critical. Recent studies isolated the cDNA encoding 1 alpha-hydroxylase from several species, and revealed that this enzyme belongs to a member of the cytochrome p450 enzyme superfamily, with highest homologies to the p450 hydroxylases for vitamin D derivatives. One of three kinds of hereditary rickets (vitamin D-dependent rickets type I) displays an autosomal recessive trait and clinical features consistent with a defect of 1 alpha-hydroxylase activity, and the genetic analysis of the type I patients identified missense mutations of the 1 alpha(OH)ase gene that results in a loss of this enzymatic activity.