Functional Analyses of a Novel Missense and Other Mutations of the Vitamin D Receptor in Association with Alopecia

This study investigated a novel mutation, S360P, in the vitamin D receptor (VDR) gene associated with hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) and alopecia in a 2-year-old girl. Despite predictions that S360P was not disease-causing, functional analyses showed disrupted transcriptional activity similar to other mutations like Q152X, R274L, and H305Q. The mutation led to a lack of ligand binding affinity, no interaction with cofactors or RXR, and impaired nuclear localization signals. The findings supported the importance of DNA binding by the VDR/RXR heterodimer for VDR function in hair development, highlighting that a single amino acid substitution could significantly disrupt protein function.