Thus, our studies have identified a pathogenic PHEX mutation in a sporadic case of adult-onset hypophosphatemic osteomalacia, and these findings highlight a role for PHEX gene analysis in some cases of suspected TIO, particularly when no tumor has been identified.
These studies indicate that mutations in the PHEX gene are unlikely to be responsible for OOM and suggest that the tumor-derived factor that inhibits phosphate uptake is a small protein that does not downregulate type II NaPi mRNA, and requires an intact cytoskeleton and protein synthesis for activity.
HMS-97 cells might be useful for further studies that aim to determine the genetic mechanism that leads to the observed PHEX and FGF-23 expression, both of which might have a direct role in the pathogenesis of oncogenic osteomalacia.
PHEX gene and hypophosphatemia.X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) are diseases that have in common abnormal proximal renal tubular function resulting in increased renal clearance of inorganic phosphorus and hypophosphatemia.
Hypophosphatemia and other biochemical abnormalities in TIO are due to excessive production of "phosphatonin" with normal PHEX function, whereas the biochemical abnormalities in XLH are caused by a mutant PHEX enzyme that fails to process "phosphatonin."
We propose unifying hypotheses for the pathogenesis of oncogenic osteomalacia and X-linked hypophosphataemic rickets which involve defects in the PEX gene.