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

July 2017 in “ Scientific Reports ”

Tamura Mayuko, Ishizawa, Michiyasu, Isojima Tsuyoshi, Ãzen, Samim, Oka Akira, Makishima Makoto, Kitanaka Sachiko, Özen Samim

vitamin D receptor VDR alopecia 1,25-dihydroxyvitamin D-resistant rickets HVDRR S360P mutation Q152X mutation R274L mutation H305Q mutation ligand binding affinity RXR nuclear localization signals VDR/RXR heterodimer rickets

TLDR A single amino acid change in the vitamin D receptor can disrupt its function and lead to hair loss.

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.