THE CLINICAL AND GENETIC ANALYSIS OF AUTOSOMAL DOMINANT HYPOPHOSPHATEMIC RICKETS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。常染色体显性低磷血症佝偻病（ADHR）是一种以孤立性肾磷消耗为特征的遗传性疾病。ADHR代表了一种“自然实验”，在这种实验中，异常的肾脏磷酸盐转运扰乱了磷酸盐稳态，导致磷酸盐浪费和随后的低磷血症。虽然这种疾病的标志是孤立的磷酸盐消耗，但磷酸盐消耗缺陷的病因尚不清楚。我们最近描述了该疾病的临床表现，并将ADHR基因位点定位在染色体12p13上。本研究的目的是利用定位克隆技术鉴定导致这种疾病的基因。为了实现我们的目标，我们将1)对ADHR家族进行表型表征并获得DNA；2)高分辨率定位疾病基因；3)分离克隆该基因。该基因的鉴定将提供对磷酸盐稳态控制的深入了解，并有助于提高对该疾病发病机制的理解。提高对ADHR病理生理学的理解可能会导致设计更好的治疗策略

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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