Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets with Alopecia in Four Egyptian Families: Report of Three Novel Mutations in the Vitamin D Receptor Gene

The study investigated the vitamin D receptor (VDR) gene in five Egyptian patients with hereditary vitamin D-resistant rickets, characterized by severe rickets, hypocalcemia, hypophosphatemia, total alopecia, and elevated serum levels of 1,25-dihydroxyvitamin D. DNA analysis revealed three novel mutations (p.Y295X, p.R343C, and p.R391H) and one previously known mutation (p.R30X) in four patients, with no mutations found in one patient. These mutations were found only in affected individuals and not in unaffected family members or 200 ethnically matched chromosomes. The mutations were expected to render the VDR nonfunctional. Treatment with high doses of oral calcium and calcidol was effective in all patients, but hair growth was observed in only one patient.