Serum phosphate concentrations are regulated by a complex and poorly understood process. Insight into this process can be obtained by analysis of genetic aberrations in phosphate homeostasis. Autosomal dominant hypophosphatemic rickets (ADHR) is an inherited disorder characterized by renal phosphate wasting and consequent hypophosphatemia that results in severe bone pain, fracture, lower extremity deformity, and short stature in affected individuals. The etiology of the phosphate wasting defect is unknown. The ADHR gene locus has been mapped to chromosome 12p13 and the goal of our study is to identify the gene responsible for the disorder using positional cloning techniques.
The specific aims proposed to attain this goal are: 1) To narrow the ADHR region using linkage analysis and deletion analysis of DNA from affected individuals; 2) To identify candidate genes within the ADHR interval; and 3) To identify the ADHR gene by detecting a disease specific alteration in one of these candidates. Identification of the gene will provide insight into the control of phosphate homeostasis and lead to an improved understanding of the pathogenesis of this disease.
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