title: Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).
abstract: 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 NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.
authors.affiliation: Department of Medicine, Université de Montréal, Canada; Department of Molecular and Integrative Physiology, Université de Montréal, Canada; Hôpital du Sacré-Coeur de Montréal, 5400 Boul. Gouin Ouest, Montréal, QC, Canada H4J 1C5. Electronic address: daniel.bichet@umontreal.ca.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
authors.affiliation: UCL Institute of Child Health, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Electronic address: d.bockenhauer@ucl.ac.uk.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics*; D018500:Diabetes Insipidus, Nephrogenic / Q000175:diagnosis / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D009154:Mutation; D017483:Receptors, Vasopressin / Q000235:genetics*
chemical_list: C496023:AQP2 protein, human; C585768:AVPR2 protein, human; D051399:Aquaporin 2; D017483:Receptors, Vasopressin
keywords: AQP2; AVPR2; Autosomal recessive nephrogenic diabetes insipidus; Cyclic AMP; Dehydration; Misfolded proteins; Nephrogenic diabetes insipidus; X-linked nephrogenic diabetes insipidus