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Vasopressin receptor mutations causing nephrogenic diabetes insipidus
D G Bichet1, M Turner, D Morin
1Department of Medecine, Université de Montréal and Research Center, Hôpital du Sacré-Coeur de Montréal, Québec, Canada.
Proceedings of the Association of American Physicians
|October 2, 1998
Summary
Congenital nephrogenic diabetes insipidus results from mutations in the AVPR2 or AQP2 genes. Most cases involve AVPR2 gene mutations, leading to non-functional vasopressin receptors and impacting water reabsorption.
Area of Science:
- Genetics
- Endocrinology
- Nephrology
Background:
- Congenital nephrogenic diabetes insipidus (cNDI) is a rare disorder characterized by renal collecting duct resistance to antidiuretic hormone.
- This resistance stems from genetic mutations affecting either the arginine vasopressin receptor 2 (AVPR2) or the aquaporin 2 (AQP2) water channel.
Purpose of the Study:
- To elucidate the genetic basis of congenital nephrogenic diabetes insipidus.
- To understand the functional consequences of identified mutations in AVPR2 and AQP2 genes.
Main Methods:
- Genetic analysis of 115 families with cNDI to identify mutations in AVPR2 and AQP2 genes.
- In vitro studies to assess the function of mutant AVPR2 receptors, including their trafficking, ligand binding, and signaling capabilities.
Main Results:
- Mutations in the AVPR2 gene account for the majority (>90%) of cNDI cases (105 out of 115 families).
- Mutations in the AQP2 gene were identified in 10 families.
- Most AVPR2 mutations result in intracellular receptor trapping or impaired cell surface expression, leading to a loss of function. A few mutations were associated with milder phenotypes.
Conclusions:
- Genetic identification of AVPR2 and AQP2 mutations is crucial for diagnosing cNDI.
- Understanding mutation-specific effects aids in developing diagnostic tools for carrier and perinatal testing.