DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.
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.
Lorenz-Depiereux
Bettina
B
Institute of Human Genetics, GSF National Research Center for Environment and Health, 85764 Munich-Neuherberg, Germany.
Bastepe
Murat
M
Benet-Pagès
Anna
A
Amyere
Mustapha
M
Wagenstaller
Janine
J
Müller-Barth
Ursula
U
Badenhoop
Klaus
K
Kaiser
Stephanie M
SM
Rittmaster
Roger S
RS
Shlossberg
Alan H
AH
Olivares
José L
JL
Loris
César
C
Ramos
Feliciano J
FJ
Glorieux
Francis
F
Vikkula
Miikka
M
Jüppner
Harald
H
Strom
Tim M
TM
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
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