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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Bone Matrix / metabolism*
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Child
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Extracellular Matrix Proteins / genetics*
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Extracellular Matrix Proteins / metabolism
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Extracellular Matrix Proteins / physiology
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Fibroblast Growth Factor-23
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Fibroblast Growth Factors / genetics
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Fibroblast Growth Factors / metabolism
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Homeostasis
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Humans
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Hypophosphatemia / genetics*
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Infant
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Mutation
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PHEX Phosphate Regulating Neutral Endopeptidase / genetics
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PHEX Phosphate Regulating Neutral Endopeptidase / metabolism
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Pedigree
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Phosphates / metabolism*
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Phosphoproteins / genetics*
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Phosphoproteins / metabolism
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Phosphoproteins / physiology
Substances
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DMP1 protein, human
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Extracellular Matrix Proteins
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FGF23 protein, human
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Phosphates
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Phosphoproteins
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Fibroblast Growth Factors
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Fibroblast Growth Factor-23
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PHEX Phosphate Regulating Neutral Endopeptidase
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PHEX protein, human