DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

  • Nat Genet. 2006 Nov;38(11):1248-50. doi: 10.1038/ng1868.
Bettina Lorenz-Depiereux  1 ,  Murat Bastepe ,  Anna Benet-Pagès ,  Mustapha Amyere ,  Janine Wagenstaller ,  Ursula Müller-Barth ,  Klaus Badenhoop ,  Stephanie M Kaiser ,  Roger S Rittmaster ,  Alan H Shlossberg ,  José L Olivares ,  César Loris ,  Feliciano J Ramos ,  Francis Glorieux ,  Miikka Vikkula ,  Harald Jüppner ,  Tim M Strom
Affiliations
  • 1. Institute of Human Genetics, GSF National Research Center for Environment and Health, 85764 Munich-Neuherberg, Germany.
PMID: 17033625 DOI: 10.1038/ng1868
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.