Objective: To study the vitamin D receptor (VDR) gene in five Egyptian patients with severe rickets and the clinical features of hereditary vitamin D-resistant rickets, including hypocalcemia, hypophosphatemia, total alopecia, and elevated serum levels of 1,25-dihydroxyvitamin D.
Study design: We amplified and sequenced DNA samples from blood from the patients, their parents, and available family members.
Results: DNA sequence analyses of the VDR gene showed three novel mutations (p.Y295X, p.R343C, and p.R391H) and a previously reported one (p.R30X) in four patients, whereas no mutation was found in one patient. Mutations cosegregated perfectly with affected individuals in all families, and did not exist in unaffected family members or 200 ethnically matched chromosomes.
Conclusion: Three novel deleterious mutations in the VDR ligand-binding domain were identified, which are expected to render the VDR nonfunctional. Successful treatment with frequent high doses of oral calcium and calcidol was evident in all patients; however, hair growth occurred only in one patient.