Hypophosphatemia due to isolated renal phosphate wasting is a genetically 
heterogeneous disease. Two new genes linked to two different forms of hereditary 
hypophosphatemias have recently been described. Autosomal recessive form of 
hypophosphatemic rickets was mapped to chromosome 4q21 and identified homozygous 
mutations in dentin matrix protein 1 (DMP1) gene, which encodes a 
non-collagenous bone matrix protein. Intact plasma levels of the phosphaturic 
protein FGF23 (fibroblast growth factor 23) were clearly elevated in some of the 
affected individuals, providing a possible explanation for the phosphaturia and 
inappropriately normal 1,25(OH)2D levels, and suggesting that DMP1 may regulate 
FGF23 expression. Hereditary hypophosphatemic rickets with hypercalciuria is 
another rare disorder of autosomal recessive inheritance. Affected individuals 
present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D 
levels and increased intestinal calcium absorption. The disease was mapped to a 
1.6 Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the 
renal sodium-phosphate cotransporter NaPi-IIc. This was the first demonstration 
that NaPi-IIc has a key role in the regulation of phosphate homeostasis. Thus, 
DMP1 and NaPi-IIc add two new members to the bone-kidney axis proposed since it 
was discovered that the first phosphatonin, FGF23, was of osteoblastic/osteocyte 
origin. This provides a mechanism for the skeleton to communicate with the 
kidney to coordinate the mineralization of extracelular matrix and the renal 
handling of phosphate.