Correlation between AVPR2 mutations and urinary AQP2 excretion in patients with nephrogenic diabetes insipidus.
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.
Kotnik
Primoz
P
Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, Vrazov trg 1, SI-1000 Ljubljana, Slovenia. primoz.kotnik@mf.uni-lj.si
Battelino
Tadej
T
Debeljak
Marusa
M
Podkrajsek
Katarina Trebusak
KT
Waldhauser
Franz
F
Frøkiaer
Jørgen
J
Nielsen
Søren
S
Krzisnik
Ciril
C
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*
D051399:Aquaporin 2; D017483:Receptors, Vasopressin