POSITIONAL CLONING OF THE PEX GENE - NEW INSIGHTS INTO THE PATHOPHYSIOLOGY OF X-LINKED HYPOPHOSPHATEMIC RICKETS

X-linked hypophosphatemic rickets (HYP) is the most common form of her editary renal phosphate wasting. The hallmarks of this disease are iso lated renal phosphate wasting with inappropriately normal calcitriol c oncentrations and a mineralization defect in bone. Studies in the Hyp mouse, one of the murine models of the human disease, suggest that the re is an similar to 50% decrease in both message and protein of NPT-2, the predominant sodium-phosphate cotransporter in the proximal tubule . However, human NPT-S maps to chromosome 5q35, indicating that it is not the disease gene. Positional cloning studies have led to the ident ification of a gene, PEX, which is responsible for the disorder. Furth er studies have led to identification of the murine Per gene, which is mutated in the murine models of the disorder. These studies, in conce rt with other studies, have led to improved understanding of the patho physiology of HYP and a new appreciation for the complexity of normal phosphate homeostasis.