Title: The role of DMP1 in autosomal recessive hypophosphatemic rickets.
Abstract: Heritable disorders of disturbed phosphate handling are the most common causes of rickets and osteomalacia in developed countries. However, the molecular mechanisms underlying skeletal mineralization are complex, and our current models are far from complete. Isolated renal phosphate wasting and subsequent low serum phosphate concentrations may result from a number of genetic disorders that include: autosomal dominant hypophosphatemic rickets (ADHR), Xlinked hypophosphatemic rickets (XLH), and hereditary hypophosphatemic rickets with hypercalciuria (HHRH).An acquired disorder of isolated renal phosphate wasting with similar phenotypes to these heritable disorders has also been recognized, tumor-induced osteomalacia (TIO). Seminal findings have confirmed an important role for the endocrine molecule, Fibroblast growth factor-23 (FGF23), identified in autosomal dominant hypophosphatemic rickets (ADHR), as playing a central role in X-linked hypophosphatemic rickets (XLH; due to inactivating mutations in the PHEX gene) 1 . Unexpectedly, mice lacking dentin matrix protein-1 (Dmp1, a non-collagenous matrix protein) were shown to have an overlapping phenotype with ADHR and XLH patients, as well as the XLH model, the Hyp mouse, manifesting hypophosphatemic rickets/osteomalacia and elevated FGF23. Building upon our work regarding the molecular genetics of disorders involving FGF23, we undertook a study to identify a novel disorder of phosphate homeostasis. We identified two unrelated consanguineous kindreds (Families 1 and 2) with hypophosphatemic rickets in the absence of hyper
Publication Year: 2007
Publication Date: 2007-12-21
Language: en
Type: article
Indexed In: ['pubmed']
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Cited By Count: 7
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