Autosomal recessive hypophosphataemic rickets with hypercalciuria is not caused by mutations in the type II renal sodium/phosphate cotransporter gene

Background. At present the genetic defect for autosomal recessive and autosomal dominant hypophosphataemic rickets with hypercalciuria (HHRH) is unknown. Type II sodium/phosphate cotransporter (NPT2) gene is a serious candidate for being the causative gene in either or both autosomal recessive and autosomal dominant HHRH. In the present study we tested this hypothesis in one autosomal recessive family. Methods. The gene structure of human NPT2 is known. We tested the complete open reading frame in the affected siblings by polymerase chain reaction in combination with automatic DNA sequencing for the presence of mutations. Results. We did not observe disease-causing mutations in the NPT2 gene of the affected siblings. A T855C polymorphism resulting in a histidine to arginine transition was present in the open reading frame of NPT2. The polymorphism was present in both affected as well as unaffected family members. Conclusion. The hypothesis that a defect in the NPT2 gene could be an underlying cause for autosomal recessive HHRH could not be sustained in our study.