Tryptophan Missense Mutation in the Ligand-Binding Domain of the Vitamin D Receptor Causes Severe Resistance to 1,25-Dihydroxyvitamin D
September 2002
in “
Journal of Bone and Mineral Research
”
New to Vitamin D? There is a guide in the encyclopedia. Read the guide → Studysummary This study found that a specific VDR amino acid substitution in children with hereditary vitamin D-resistant rickets disrupts ligand binding and gene activation but does not impair hair follicle development.
Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer
In this study, two siblings exhibited severe vitamin D-resistant rickets without alopecia due to a tryptophan to arginine substitution at amino acid 286 in the vitamin D receptor (VDR). Despite normal VDR protein and mRNA expression, their fibroblasts could not bind 1,25-dihydroxyvitamin D3, and the mutation abolished the 24-hydroxylase gene response. This highlighted the critical role of the VDR tryptophan in ligand binding and gene transactivation, essential for calcium homeostasis and bone mineralization, while suggesting that a stable VDR-bound ligand might not be necessary for normal hair follicle development.
