title: [From gene to disease; hypophosphataemic rickets and the PHEX gene].
abstract: X-linked hypophosphataemic rickets is associated with mutations in the PHEX gene on the short arm of the X chromosome, encoding a membrane-bound endoprotease which is predominantly expressed in osteoblasts. Defective PHEX function leaves phosphaturic peptides such as FGF23 uncleaved, enabling these peptides, known as phosphatonins, to fully exert their phosphaturic potential in the proximal tubule of the kidney. An autosomally inherited form of hypophosphataemic rickets is caused by mutations in the proteolytic processing site of FGF23 itself, while in tumour-induced osteomalacia overproduction of FGF23 and possibly other phosphatonins causes the processing capacity to be exceeded, resulting in phosphaturic hypophosphataemia and osteomalacia.
authors.affiliation: Universitair Medisch Centrum Utrecht, locatie Wilhelmina Kinderziekenhuis.
authors.forename: M
authors.initials: M
authors.lastname: Jansen
authors.forename: C M L
authors.initials: CM
authors.lastname: van Dael
authors.forename: A A
authors.initials: AA
authors.lastname: Verrijn Stuart
authors.forename: A H
authors.initials: AH
authors.lastname: van der Hout
authors.forename: P
authors.initials: P
authors.lastname: Rump
mesh_terms: D041321:Chromosomes, Human, X / Q000235:genetics*; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010710:Phosphates / Q000502:physiology*
chemical_list: C000717427:FGF23 protein, human; D008562:Membrane Glycoproteins; D010710:Phosphates; D000089703:Fibroblast Growth Factor-23; D008666:Metalloendopeptidases; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human