Novel Vitamin D Receptor Mutations in Hereditary Vitamin D Resistant Rickets in Chinese

The study described a case of a female toddler with hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR), characterized by severe rickets, hypocalcemia, and hypophosphatemia, but notably without alopecia. Genetic analysis identified novel compound heterozygous mutations in the VDR gene: p.M4I and p.H229Q. The p.M4I mutation, in combination with FOKI-F, eliminated both translation start sites of the VDR protein, while the p.H229Q mutation resulted in significantly reduced VDR transactivation activity despite normal dimerization with RXR. This report expanded the known mutation spectrum of HVDRR and highlighted the first case where a benign variant p.M4I, along with a common p.M1T polymorphism, contributed to a pathogenic allele.