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Human Genetics

, Volume 98, Issue 5, pp 587–589 | Cite as

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

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.

Keywords

Codon Diabetes Insipidus Splice Donor Splice Donor Site Nephrogenic Diabetes Insipidus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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

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