title: Correlation between AVPR2 mutations and urinary AQP2 excretion in patients with nephrogenic diabetes insipidus.
abstract: Activation of the V2 receptor by arginine vasopressin (AVP) results in trafficking of the water channel AQP2 to the luminal plasma membrane and a small amount into the urine. Mutations in the A VPR2 gene, encoding the AVP V2 receptor, result in congenital nephrogenic diabetes insipidus (CNDI). To determine a correlation between A VPR2 mutations and urinary AQP2 excretion, immunobloting was used to detect AQP2 in the urine of patients with CNDI before and after a dehydration test. The patients' genotype was determined using PCR amplification and direct sequencing of the complete A VPR2 gene. Urinary AQP2 excretion was absent in patients with severely debilitating mutations, a novel total deletion of the A VPR2 gene, and a novel nonsense mutation W296X. However, it was detected in siblings with a V88M missense mutation. Urinary AQP2 excretion correlated well with other tested phenotype markers. Urinary AQP2 excretion could be used to evaluate the remaining in vivo integrity of the AVP-V2 receptor-AQP2 cascade in patients with CNDI.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, Vrazov trg 1, SI-1000 Ljubljana, Slovenia. primoz.kotnik@mf.uni-lj.si
authors.forename: Primoz
authors.initials: P
authors.lastname: Kotnik
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.forename: Marusa
authors.initials: M
authors.lastname: Debeljak
authors.forename: Katarina Trebusak
authors.initials: KT
authors.lastname: Podkrajsek
authors.forename: Franz
authors.initials: F
authors.lastname: Waldhauser
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Ciril
authors.initials: C
authors.lastname: Krzisnik
mesh_terms: D000293:Adolescent; D000328:Adult; D051399:Aquaporin 2 / Q000652:urine*; D002675:Child, Preschool; D003681:Dehydration / Q000235:genetics; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics* / Q000652:urine*; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D017483:Receptors, Vasopressin / Q000235:genetics*
chemical_list: D051399:Aquaporin 2; D017483:Receptors, Vasopressin