THE CLINICAL AND GENETIC ANALYSIS OF AUTOSOMAL DOMINANT HYPOPHOSPHATEMIC RICKETS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 常染色体显性遗传性低磷血症性软骨病(ADHR)是一种以孤立的肾脏磷酸盐消耗为特征的综合性疾病。ADHR代表了一种“自然实验”，在这种实验中，肾脏磷酸盐转运异常扰乱了磷酸盐的动态平衡，导致了磷酸盐的浪费和随后的低磷血症。虽然这种疾病的特征是孤立的磷酸盐消耗，但磷酸盐消耗缺陷的病因尚不清楚。我们最近描述了这种疾病的临床表现，并将ADHR基因定位在染色体12p13上。本研究的目的是利用位置克隆技术确定导致这种疾病的基因。为了实现我们的目标，我们将1)从ADHR家族中提取DNA；2)高分辨率地定位疾病基因；3)分离和克隆该基因。该基因的鉴定将有助于深入了解磷酸盐稳态的控制，并有助于更好地理解这种疾病的发病机制。对ADHR病理生理学的更好理解可能会导致设计出更好的治疗策略。

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 integrated 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.