A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2.
Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls.
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark ghinrichs@health.sdu.dk.
Gitte R
GR
Hinrichs
Anaesthesiology and Intensive Care, Odense University Hospital, Odense, Denmark.
Louise H
LH
Hansen
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Maria R
MR
Nielsen
Clinical Genetics, Odense University Hospital, Odense, Denmark.
Christina
C
Fagerberg
Department of Nephrology, Odense University Hospital, Odense, Denmark.
Hans
H
Dieperink
Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
Søren
S
Rittig
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Boye L
BL
Jensen
D051399:Aquaporin 2 / Q000652:urine*; D001120:Arginine / Q000235:genetics; D015153:Blotting, Western; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D055354:Exosomes / Q000378:metabolism; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D017483:Receptors, Vasopressin / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics*; D055815:Young Adult
C585768:AVPR2 protein, human; D051399:Aquaporin 2; D017483:Receptors, Vasopressin; D001120:Arginine
ALIX; dehydration; receptor; vasopressin