Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus

Daniel G. Bichet, Mariel Birnbaumer, Michèle Lonergan, Marie Françoise Arthus, Walter Rosenthal, Paul Goodyer, Hubert Nivet, Stéphane Benoit, Philip Giampietro, Simonetta Simonetti, Alfred Fish, Chester B. Whitley, Philippe Jaeger, Joseph Gertner, Maria New, Francis J. DiBona, Bernard S. Kaplan, Gary L. Robertson, Geoffrey N. Hendy, T. Mary FujiwaraKenneth Morgan

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127 Scopus citations


X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine-vasopressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. We analyzed 31 independent NDI families to determine the nature and recurrence of AVPR2 mutations. Twenty- one new putative disease-causing mutations were identified: 113delCT, 253del35, 255del9, 274insG, V88M, R106C, 402delCT, C112R, Y124X, S126F, W164S, S167L, 684delTA, 804insG, W284X, A285P, W293X, R337X, and three large deletions or gene rearrangements. Five other mutations-R113W, Y128S, R137H, R181C, and R202C-that previously had been reported in other families were detected. There was evidence for recurrent mutation for four mutations (R113W, R137H, S167L, and R337X). Eight de novo mutation events were detected (274insG, R106C, Y128S, 167L [twice], R202C, 684delTA, and R337X). The origins were maternal (one), grandmaternal (one), and grandpaternal (six). In the 31 NDI families and 6 families previously reported by us, there is evidence both for mutation hot spots for nucleotide substitutions and for small deletions and insertions. More than half (58%) of the nucleotide substitutions in 26 families could be a consequence of 5-methyl-cytosine deamination at a CpG dinucleotide. Most of the small deletions and insertions could be attributed to slipped mispairing during DNA replication.

Original languageEnglish (US)
Pages (from-to)278-286
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number2
StatePublished - 1994

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