The molecular basis of vitamin D-dependent rickets type I.

Vitamin D 1alpha-hydroxylase is a key enzyme for the vitamin D-calcium homeostasis. Recently, 1alpha-hydroxylase cDNA and gene were cloned. Human 1alpha-hydroxylase gene is located at chromosome 12q13.3. Several inactivating mutations in the 1alpha-hydroxylase gene were found in VDDR I patients, and it was established that 1alpha-hydroxylase gene is responsible for VDDR I. To date, various mutations spreading over all exons have been reported. The cloning of 1alpha-hydroxylase gene will further lead to the better understanding of vitamin D regulation in both normal and pathological states. In addition, 1alpha-hydroxylase knock-out mice, which is recently generated, would be a useful model animal for VDDR I.