title: DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.
abstract: Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four 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.
authors.affiliation: Institute of Human Genetics, GSF National Research Center for Environment and Health, 85764 Munich-Neuherberg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Lorenz-Depiereux
authors.forename: Murat
authors.initials: M
authors.lastname: Bastepe
authors.forename: Anna
authors.initials: A
authors.lastname: Benet-Pagès
authors.forename: Mustapha
authors.initials: M
authors.lastname: Amyere
authors.forename: Janine
authors.initials: J
authors.lastname: Wagenstaller
authors.forename: Ursula
authors.initials: U
authors.lastname: Müller-Barth
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Kaiser
authors.forename: Roger S
authors.initials: RS
authors.lastname: Rittmaster
authors.forename: Alan H
authors.initials: AH
authors.lastname: Shlossberg
authors.forename: José L
authors.initials: JL
authors.lastname: Olivares
authors.forename: César
authors.initials: C
authors.lastname: Loris
authors.forename: Feliciano J
authors.initials: FJ
authors.lastname: Ramos
authors.forename: Francis
authors.initials: F
authors.lastname: Glorieux
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
mesh_terms: D000293:Adolescent; D000328:Adult; D001857:Bone Matrix / Q000378:metabolism*; D002648:Child; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D017674:Hypophosphatemia / Q000235:genetics*; D007223:Infant; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010710:Phosphates / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; D010710:Phosphates; D010750:Phosphoproteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human