Human Genetics

, Volume 98, Issue 5, pp 587–589

Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus

  • Alexander Oksche
  • Andreas Möller
  • John Dickson
  • Werner Rosendahl
  • Wolfgang Rascher
  • Daniel G. Bichet
  • W. Rosenthal
Original investigation

DOI: 10.1007/s004390050264

Cite this article as:
Oksche, A., Möller, A., Dickson, J. et al. Hum Genet (1996) 98: 587. doi:10.1007/s004390050264

Abstract

The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R gene of the patient of family 1 had the wild-type sequence. Consequently, the coding region of the aquaporin-2 gene including the exon-intron junctions was sequenced. A novel G to T transversion at codon 202, predictive of an exchange of tryptophan 202 by cysteine, was identified. As the mutation occurs at G-1 of the 5′ splice donor site of intron 3, aberrant splicing is also likely. The mutation involves one of the supposed water pore-forming loops. Therefore, both aberrant splicing and amino acid substitution are likely to result in a functionally defective protein. Sequencing of the complete V2R gene of the male patient of family 2 revealed a novel single-base deletion at codon 310 (ΔC1001), shifting the reading frame to give an altered amino acid sequence beginning at codon 311. The mutation is unique in predicting a C-terminally extended protein (termination after codon 434 in the mutant receptor instead of codon 371 in the wild-type). The deduced mutant protein is likely to be nonfunctional since the amino acid sequence of the seventh transmembrane domain and the C-terminus is altered.

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • Alexander Oksche
    • 1
  • Andreas Möller
    • 1
  • John Dickson
    • 1
  • Werner Rosendahl
    • 2
  • Wolfgang Rascher
    • 3
  • Daniel G. Bichet
    • 4
  • W. Rosenthal
    • 1
  1. 1.Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Frankfurter Str. 107, D-35392 Giessen, Germany Tel.: +49-641-702-41-35; Fax: +49-641-702-41-33DE
  2. 2.Kinderklinik, Eberhard-Karls-Universität Tübingen, D-72070 Tübingen, GermanyDE
  3. 3.Zentrum für Kinderheilkunde, Justus-Liebig-Universität Giessen, D-35392 Giessen, GermanyDE
  4. 4.Centre du Recherches, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec H4J 1C5, CanadaCA