Diversity of Nephrogenic Diabetes Insipidus Mutations and Importance of Early Recognition and Treatment
|Title:||Diversity of Nephrogenic Diabetes Insipidus Mutations and Importance of Early Recognition and Treatment|
|Authors:||Bichet, Daniel G.; Fujiwara, T. Mary|
|Publisher:||Clinical and Experimental Nephrology|
Reports of 85 different putative disease-causing mutations in the AVPR2 gene, in 123 unrelated families with X-linked nephrogenic diabetes insipidus, have now been published. Of these, 19 disease-causing mutations were identified in ancestrally independent Japanese families. When studied in vitro, most AVPR2 mutations lead to receptors that are trapped intracellulary, and that are unable to reach the plasma membrane. A minority of the mutant receptors reach the cell surface, but are unable to bind arginine vasopressin, or to trigger an intracellular cyclic adenosine monophosphate (cAMP) signal. Similarly, AQP2 mutant proteins are trapped intracellularly, and cannot be expressed at the luminal membrane. This APQ2 trafficking defect is correctable, at least in vitro, by chemical chaperones.