title: Familial tumoral calcinosis and the role of O-glycosylation in the maintenance of phosphate homeostasis.
abstract: Familial tumoral calcinosis refers to a group of disorders inherited in an autosomal recessive fashion. Hyperphosphatemic tumoral calcinosis is characterized by increased re-absorption of phosphate through the renal proximal tubule, resulting in elevated phosphate concentration and deposition of calcified deposits in cutaneous and subcutaneous tissues, as well as, occasionally, in visceral organs. The disease was found to result from mutations in at least 3 genes: GALNT3, encoding a glycosyltransferase termed ppGalNacT3, FGF23 encoding a potent phosphaturic protein, and KL encoding Klotho. Recent data showed that ppGalNacT3 mediates O-glycosylation of FGF23, thereby allowing for its secretion and possibly protecting it from proteolysis-mediated inactivation. Klotho was found to serve as a co-receptor for FGF23, thereby integrating the genetic data into a single physiological system. The elucidation of the molecular basis of HFTC shed new light upon the mechanisms regulating phosphate homeostasis, suggesting innovative therapeutic strategies for the management of hyperphosphatemia in common acquired conditions such as chronic renal failure.
authors.affiliation: Center for Translational Genetics, Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Chefetz
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D002114:Calcinosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000502:physiology; D006031:Glycosylation; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D054559:Hyperphosphatemia / Q000235:genetics; D000090265:Klotho Proteins; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D010710:Phosphates / Q000378:metabolism*; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D005966:Glucuronidase; D000090265:Klotho Proteins; D017350:N-Acetylgalactosaminyltransferases; D010710:Phosphates; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human