The role of vitamin D receptor mutations in the development of alopecia

• Published in: Molecular and cellular endocrinology Vol. 347; no. 1; pp. 90 - 96
• Main Authors: Malloy, Peter J., Feldman, David
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 05.12.2011
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - physiology; Abnormalities; alopecia; Alopecia - complications; Alopecia - genetics; Animals; Calcitriol; Calcium; Calcium - metabolism; Cellular; Children; DNA; Familial Hypophosphatemic Rickets - complications; Familial Hypophosphatemic Rickets - genetics; Familial Hypophosphatemic Rickets - metabolism; Hair; Hair Follicle - metabolism; hair follicles; Homeostasis; Humans; hyperparathyroidism; hypocalcemia; intestines; Metabolism; Mice; Mice, Knockout; Mutation; Mutations; Receptors; Receptors, Calcitriol - genetics; Receptors, Calcitriol - physiology; Resistance; Rickets; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; vitamin D; Vitamins; Hair; Resistance; Calcium; Rickets; Metabolism; Calcitriol
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2011.05.045

► HVDRR is a rare disease due to mutations in the vitamin D receptor (VDR) causing resistance to 1,25(OH) 2D action. ► HVDRR is characterized by hypocalcemia, rickets, hyperparathyroidism, elevated 1,25(OH) 2D, and in many cases alopecia. ► Studies in HVDRR patients and mice indicate that alopecia is associated with defects in VDR and not 1,25(OH) 2D metabolism. ► Human and mouse data suggest that defective unliganded VDR may cause alopecia via abnormal keratinocyte development. ► Mutant VDR may cause alopecia by defective gene regulation involving Wnt, hedgehog, PTHrP or other signaling pathways. Hereditary Vitamin D Resistant Rickets (HVDRR) is a rare disease caused by mutations in the vitamin D receptor (VDR). The consequence of defective VDR is the inability to absorb calcium normally in the intestine. This leads to a constellation of metabolic abnormalities including hypocalcemia, secondary hyperparathyroidism and hypophosphatemia that cause the development of rickets at an early age in affected children. An interesting additional abnormality is the presence of alopecia in some children depending on the nature of the VDR mutation. The data indicate that VDR mutations that cause defects in DNA binding, RXR heterodimerization or absence of the VDR cause alopecia while mutations that alter VDR affinity for 1,25(OH) 2D 3 or disrupt coactivator interactions do not cause alopecia. The cumulative findings indicate that hair follicle cycling is dependent on unliganded actions of the VDR. Further research is ongoing to elucidate the role of the VDR in hair growth and differentiation.