Mutations in the Vitamin D Receptor and Hereditary Vitamin D-Resistant Rickets

The document discussed mutations in the vitamin D receptor (VDR) and their role in hereditary vitamin D-resistant rickets (HVDRR). HVDRR was characterized by the body's inability to respond to vitamin D, leading to rickets despite adequate levels of the vitamin. The study identified specific mutations in the VDR gene that impaired the receptor's function, preventing normal calcium and phosphate metabolism. This research provided insights into the genetic basis of HVDRR and highlighted the importance of VDR in bone health. Affected children often exhibited alopecia and did not respond to calcitriol treatment, requiring high doses of calcium instead. HVDRR was an autosomal recessive disorder, with over 100 cases recorded and 45 unique mutations identified in the VDR gene. These mutations interfered with VDR's ability to bind DNA or interact with coactivators, leading to hormone resistance. The presence of alopecia was a distinguishing feature, especially in cases with DNA-binding domain mutations. The findings highlighted the critical role of VDR in intestinal calcium absorption rather than direct bone action.