Phenotypic Heterogeneity in 5 Japanese Patients with an Identical Point Mutation in the Vitamin D Receptor Gene

摘要

A boy with vitamin D-dependent rickets type II (VDDR II) is reported. He had a unique G-to-A transition at position 140 in exon 3 of the intracellular 1, 25-dihydroxyvitamin D receptor (VDR) gene. He had also very mild clinical manifestations and posed a question as to which factors might be involved in determining the clinical severity of the disease among patients with the same gene mutation.We studied the patient and further compared him to the four patients previously reported with both VDDR II and the same point mutation of the VDR gene. We found wide clinical diversity among the five patients. The severity of alopecia, rickets and resistance to vitamin D seemed to correlate with each other. Furthermore, the rate of nuclear uptake of [3H] 1, 25-dihydroxyvitamin D3 in skin fibroblasts and the serum alkaline phosphatase activity were found to correlate with clinical severity. Therefore it was concluded that the phenotypic variability observed in the five patients might be due to the involvement of a nuclear accessory factor and a nongenomic action of 1, 25-dihydroxyvitamin D.