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.
| Clinkenbeard, Erica L; White, Kenneth E (2016) Systemic Control of Bone Homeostasis by FGF23 Signaling. Curr Mol Biol Rep 2:62-71 |
| Clinkenbeard, Erica L; Cass, Taryn A; Ni, Pu et al. (2016) Conditional Deletion of Murine Fgf23: Interruption of the Normal Skeletal Responses to Phosphate Challenge and Rescue of Genetic Hypophosphatemia. J Bone Miner Res 31:1247-57 |
| Clinkenbeard, Erica L; Farrow, Emily G; Summers, Lelia J et al. (2014) Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice. J Bone Miner Res 29:361-9 |
| Koller, D L; White, K E; Liu, G et al. (2003) Linkage of structure at the proximal femur to chromosomes 3, 7, 8, and 19. J Bone Miner Res 18:1057-65 |
| White, K E; Carn, G; Lorenz-Depiereux, B et al. (2001) Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney Int 60:2079-86 |
| Rowe, P S; de Zoysa, P A; Dong, R et al. (2000) MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. Genomics 67:54-68 |
| DiMeglio, L A; White, K E; Econs, M J (2000) Disorders of phosphate metabolism. Endocrinol Metab Clin North Am 29:591-609 |
