Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia Resulting From a Novel Missense Mutation in the DNA-Binding Domain of the Vitamin D Receptor

This study investigated a young boy with hereditary vitamin D resistant rickets (HVDRR) and partial alopecia, identifying a novel missense mutation in the vitamin D receptor (VDR) gene. The mutation, V26M, was found in the DNA-binding domain of the VDR, leading to resistance to the active hormone 1,25-dihydroxyvitamin D3. Despite normal binding and expression of the mutant VDR, the patient's fibroblasts were unresponsive to high concentrations of the hormone, failing to induce CYP24A1 gene expression. The boy's condition improved with intravenous calcium therapy, normalizing his serum chemistries and bone X-rays. This mutation disrupted VDR's ability to bind to a vitamin D response element, explaining the clinical features observed.