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Study Description

  1. Several different genes cause, when mutated, increased urinary phosphate excretion and hypophosphatemia leading to rickets/osteomalacia; however, the majority of phosphate-wasting disorders has not yet been defined at the molecular level. Identification of phosphate-regulating genes has provided important novel insights into the mechanism contributing to phosphate homeostasis, which remains incompletely understood. We therefore pursue exome-wide nucleotide sequence analysis to define the underlying mutations, which is expected to provide novel insights into the regulation of this important mineral.
  2. Virtually nothing is known about the genetic mutations that cause non-syndromic structural abnormalities involving the urinary tract, which represent about 50% of the causes of end-stage renal disease (ESRD). The completion of the human genome project and the technological advances that allow low cost whole exome sequencing have now made it feasible to readily search for the cause of different inherited disorders in humans, particularly if clinical information and genomic DNA is available from larger kindreds with multiple affected members that can be used for mapping the disease-causing genetic locus. Furthermore, catalogs were generated that document the expression profiles of numerous genes during embryonic, fetal, and postnatal development, thereby supporting the exploration of kidney involvement in animal models of different diseases and in human genetic syndromes. We therefore plan to define the mechanisms leading to inherited disorders of the urogenital tract and the kidneys by establishing the causative genetic defects through a combination of genetic mapping and whole exome sequencing.
  3. Hajdu-Cheney Syndrome (HCS) is a rare autosomal-dominant skeletal disorder characterized by severe osteoporosis, acroosteolysis of the distal phalanges, renal cysts and other abnormalities. Our goal is to identify the genetic cause of HCS using exome sequencing.
  4. Opsismodysplasia is a very rare recessive spondylometaphyseal dysplasia characterized by delayed epiphyseal ossification, shortness of bones and sometimes low serum phosphate levels. Discovery of the causing mutation will give us insights into the pathogenesis of this often lethal disease.

  • Study Types: Probands, Mendelian, Family
  • Number of study subjects that have individual level data available through Authorized Access: 21

Authorized Access
Publicly Available Data (Public ftp)

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Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Exome Sequencing Agilent SureSelect Human All Exon v.2 Kit N/A N/A
Study History

  1. Subjects with familial isolated hypophosphatemic rickets who do not have mutations in the PHEX gene and their 1st degree relatives.
  2. Subjects with familial vesico-ureteral reflux disease which is not explained on the genetic level and their 1st degree relatives.
  3. Subjects with Hajdu-Cheney syndrome, sporadic or familial, and their 1st degree relatives.
  4. Subjects with opsismodysplasia and their 1st degree relatives.

Selected publications
Diseases/Traits Related to Study (MESH terms)
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Study Attribution