Mutations in the vasopressin V2 receptor gene in two families with nephrogenic diabetes insipidus

Eliezer J. Holtzman, Lee F. Kolakowski, Ossie Geifman-Holtzman, David G. O'Brien, Majid Rasoulpour, Ann P. Guillot, Dennis A. Ausiello

Research output: Contribution to journalArticlepeer-review


Congenital nephrogenic diabetes insipidus (CNDI) is a rare X-linked disorder in which the renal collecting duct is unresponsive to arginine vasopressin, and thus, the urine is consistently hypotonic to plasma. As a result, affected individuals are unable to concentrate urine and suffer from episodes of severe dehydration and hypernatremia. Recently, the association between arginine vasopressin V2 receptor gene mutations and CNDI has been demonstrated. In this report, two additional novel molecular defects of the arginine vasopressin V2 receptor gene in CNDI families are described. In one family, the affected individual demonstrated a G → T transversion causing a nonsense mutation in codon 231. This mutation results in a glutamic acid becoming a termination codon, causing premature termination and truncation of the encoded receptor protein. This mutation causes a NciI site within the gene to be abolished and a BsoWI site to be created. In the second family, affected individuals showed a 28-basepair duplicating insertion in the very beginning of exon 2 downstream of the splice acceptor site. It was hypothesized that an insertion mutagenesis mechanism involves the formation of a stem-loop structure within the newly synthesized DNA strand, followed by a slipped mispairing. This may be a general mechanism for the deletion or insertion of repeated sequences within the genome. Recent data show that G-protein-coupled receptors are susceptible to many different mutations that often result in the loss of function, causing a similar clinical phenotype.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalJournal of the American Society of Nephrology : JASN
Issue number2
StatePublished - Aug 1994
Externally publishedYes


  • Chromosome-X
  • Duplicating insertion
  • G-protein-coupled receptor
  • Hormone resistance
  • Mutagenesis


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