Nephrogenic diabetes insipidus.
Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800) who have mutations in the arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2 receptor. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800). In these families, mutations have been identified in the aquaporin-2 gene (AQP2) (OMIM 107777), which codes for the vasopressin-sensitive water channel. Most missense AVPR2 mutations lead to receptors that are trapped intracellularly; a few mutant receptors reach the cell surface but are unable to bind AVP or to properly trigger an intracellular cyclic adenosine monophosphate signal. Similarly, most AQP2 mutant proteins are also misrouted. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value because early diagnosis and treatment can avert the physical and mental retardation associated with repeated episodes of dehydration.
Bichet
Daniel G
DG
Centre de Recherche, Hôpital du Sacré-Couer de Montréal, Montreal, Quebec, Canada. Daniel.bichet@umontreal.ca
D051399:Aquaporin 2 / Q000235:genetics*; D001127:Arginine Vasopressin / Q000235:genetics; D004247:DNA / Q000235:genetics; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017483:Receptors, Vasopressin / Q000235:genetics*
C496023:AQP2 protein, human; D051399:Aquaporin 2; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D004247:DNA