CLINICAL AND GENETIC ANALYSIS OF ADHR

Project: Research project

Description

The familial hypophosphatemic rachitic diseases are the most common
forms of rickets/osteomalacia in developed countries. The three
forms of hereditary rickets/osteomalacia: X-linked hypophosphatemic
rickets (XLH), hereditary hypophosphatemic rickets with
hypercalciuria (HHRH) and autosomal dominant hypophosphatemic
rickets (ADHR) are inherited in an X-linked dominant, autosomal
recessive and autosomal dominant mode, respectively. These
distinct disorders have different clinical presentations, although
in each case abnormal renal phosphate transport disturbs phosphate
homeostasis and results in renal phosphate wasting and consequent
hypophosphatemia. Thus, these disorders are 'experiments of
nature' in which mutations have arisen in genes that play important
roles in phosphate homeostasis. The goals of this study are to
characterize the phenotypic abnormalities in ADHR, the disorder
about which least is known, and to isolate the gene responsible for
this disorder. To accomplish these goals we will evaluate affected
individuals clinically, biochemically and radiographically and use
positional cloning techniques to eventually clone the disease gene.
Initially, we will employ linkage analysis in kindreds with ADHR to
localize the disease gene to an autosome. Subsequently, we will
determine a more detailed genetic map of the area around the ADHR
gene. Once a detailed genetic map of the region is determined, we
will eventually clone the ADHR gene using fine structure mapping
techniques. Successful completion of this study will not only
characterize a poorly understood disease, but will allow
elucidation of the pathogenesis of the renal phosphate wasting in
this disorder and increase our understanding of phosphate
homeostasis.
StatusFinished
Effective start/end date8/1/936/30/16

Funding

  • National Institutes of Health: $261,225.00
  • National Institutes of Health: $277,135.00
  • National Institutes of Health: $325,987.00
  • National Institutes of Health: $110,050.00
  • National Institutes of Health: $300,491.00
  • National Institutes of Health: $316,214.00
  • National Institutes of Health: $346,500.00
  • National Institutes of Health
  • National Institutes of Health: $331,100.00
  • National Institutes of Health: $332,640.00
  • National Institutes of Health: $306,837.00
  • National Institutes of Health: $101,005.00
  • National Institutes of Health: $332,640.00
  • National Institutes of Health: $329,802.00
  • National Institutes of Health
  • National Institutes of Health: $269,063.00
  • National Institutes of Health: $257,121.00
  • National Institutes of Health: $316,008.00
  • National Institutes of Health: $256,306.00
  • National Institutes of Health: $107,481.00

Fingerprint

Phosphates
Familial Hypophosphatemic Rickets
Kidney
Homeostasis
Genes
Mutation
Osteomalacia
Rickets
Autosomal Dominant Hypophosphatemic Rickets
Clone Cells
Organism Cloning
Phosphorus
Animal Models
Missense Mutation
Hypophosphatemia
Organized Financing
Metabolic Bone Diseases
Developed Countries
Minerals
Dominant Genes

ASJC

  • Medicine(all)