Phenotypic Heterogeneity in Five Japanese Patients with an Identical Point Mutation in the Vitamin D Receptor Gene

The study examined 5 Japanese patients with vitamin D-dependent rickets type II (VDDR II) who shared an identical point mutation in the vitamin D receptor (VDR) gene. Despite having the same genetic mutation, the patients exhibited significant phenotypic heterogeneity, particularly in the severity of alopecia, rickets, and vitamin D resistance. The study found that the clinical severity correlated with the rate of nuclear uptake of [3H] 1, 25-dihydroxyvitamin D3 in skin fibroblasts and serum alkaline phosphatase activity. The researchers concluded that the variability in clinical manifestations might be due to a nuclear accessory factor and a nongenomic action of 1, 25-dihydroxyvitamin D.