Nature Genetics
- 38, 1248 - 1250 (2006)
Published online: 8 October 2006; | doi:10.1038/ng1868
DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasisBettina Lorenz-Depiereux1, 12, Murat Bastepe2, 12, Anna Benet-Pagès1, Mustapha Amyere3, Janine Wagenstaller1, Ursula Müller-Barth4, Klaus Badenhoop5, Stephanie M Kaiser6, Roger S Rittmaster6, Alan H Shlossberg6, José L Olivares7, César Loris8, Feliciano J Ramos7, Francis Glorieux9, Miikka Vikkula3, Harald Jüppner2, 10 & Tim M Strom1, 111
Institute of Human Genetics, GSF National Research Center for Environment and Health, 85764 Munich-Neuherberg, Germany. 2
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. 3
Human Molecular Genetics (GEHU), Christian de Duve Institute & Université catholique de Louvain, 1200 Brussels, Belgium. 4
Medical Genetics, 63450 Hanau, Germany. 5
Division of Endocrinology, Diabetes and Metabolism, University Hospital, 60590 Frankfurt am Main, Germany. 6
Division of Endocrinology and Metabolism, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada. 7
Department of Pediatrics, University Hospital Lozano Blesa, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain. 8
Service of Nephrology, University Children's Hospital Miguel Servet, 50009 Zaragoza, Spain. 9
Shriners Hospital for Children, Genetics Unit, Montreal, Canada. 10
Pediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. 11
Institute of Human Genetics, Klinikum rechts der Isar, Technical University, 81675 Munich, Germany. 12
These authors contributed equally to this work.
Correspondence should be addressed to Tim M Strom TimStrom@gsf.de or Harald Jüppner jueppner@helix.mgh.harvard.edu DMP1FGF23DMP1Hypophosphatemia 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.
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