CLINICAL AND GENETIC ANALYSIS OF ADHR

Indiana Univ-Purdue Univ At Indianapolis, Indianapolis IN

Investigators

Linked publications & trials

Abstract

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 isolated renal phosphate wasting. ADHR represents an "experiment of nature" in which abnormal renal phosphate transport disturbs phosphate homeostasis and results in phosphate wasting and consequent hypophosphatemia. Although the hallmark of the disorder is isolated phosphate wasting the etiology of the phosphate wasting defect is unknown. We have recently characterized the clinical manifestations of the disorder and mapped the ADHR gene locus to chromosome 12p13. The goal of the present study is to identify the gene responsible for the disorder using positional cloning techniques. To accomplish our goal we will 1) phenotypically characterize and obtain DNA from ADHR families; 2) map the disease gene with high resolution and 3) isolate and clone the gene. Identification of the gene will provide insight into control of phosphate homeostasis and lead to an improved understanding of the pathogenesis of this disease. Improved understanding of the pathophysiology of ADHR may lead to the design of better therapeutic strategies for the disorder.