Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: A case report and review of the literature

Vassos Neocleous, Nicos Skordis, Christos Shammas, Elisavet Efstathiou, Nikolaos P. Mastroyiannopoulos, Leonidas A. Phylactou

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

X-linked nephrogenic diabetes insipidus (NDI) is a rare disease characterized by a malfunctioning renal response to the antidiuretic hormone arginine vasopressin (AVP) due to mutations in the AVPR2 gene. A limited number of mutations in the AVPR2 gene resulting in partial phenotype have been described so far. In this mini-review the retrospective analysis of 13 known AVPR2 mutations that have been previously shown in vitro to partially abolish AVPR2 function is described, along with a novel mutation diagnosed in a kindred with partial NDI. In the present study, a 14 year old male and his 73 year old maternal grandfather were diagnosed with partial NDI based on the clinical phenotype, the water deprivation test and the inadequate response to 1-desamino-8-d-arginine vasopressin (DDAVP) administration. Sequencing analysis of the AVPR2 gene revealed the novel missense mutation p.N317S (g.1417A > G) in both patients. This mutation was re-created by site directed mutagenesis in an AVPR2 cDNA expression vector and was functionally characterized, in terms of arginine vasopressin (AVP) and DDAVP response. AVPR2 activity of the p.N317S mutant receptor after the AVP and DDAVP administration, as assessed by cAMP production was reduced and impaired when compared to cells that expressed the wild type AVPR2 gene. In conclusion, the affected members of this family have X-linked NDI with partial resistance to AVP, due to a missense mutation in the AVPR2 gene.

Original languageEnglish
Pages (from-to)922-930
Number of pages9
JournalMetabolism: Clinical and Experimental
Volume61
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • 1-desamino-8-d-arginine vasopressin
  • arginine vasopressin
  • AVP
  • DDAVP
  • NDI
  • nephrogenic diabetes insipidus

Fingerprint Dive into the research topics of 'Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: A case report and review of the literature'. Together they form a unique fingerprint.

  • Cite this