Mosaicism For A Postzygotic Avpr2 Mutation Resulting In Partial Nephrogenic Diabetes Insipidus

The objective of the study was to determine the genotype of a male patient diagnosed with a partial form of nephrogenic diabetes insipidus (NDI), a disorder characterized by renal tubular unresponsiveness to the antidiuretic hormone arginine‐vasopressin (AVP) and consequently excessive water secretion. Direct sequencing of the arginine vasopressin receptor 2 (AVPR2) gene on the X‐chromosome identified a heterozygous pattern for a point mutation (g.797G>A) in exon 2 predicting G122D amino acid substitution. Contamination was excluded by analysis of a new blood sample. Restriction enzyme analysis confirmed the results. Karyotyping excluded Klinefelter's syndrome (46, XY). No other mutations were found in the coding region of the AVPR2 or the aquaporin‐2 genes. Healthy family members were all homo‐ or hemizygous for the wildtype AVPR2 gene. The identified mutation has previously been reported as causing NDI. We conclude that this unusual finding of a heterozygous pattern in a male patient with an X‐linked disease must be due to a mosaic pattern of the AVPR2 gene as a consequence of a postzygotic mutation, the result being a partial NDI phenotype. Research Support: Novo Nordisk Foundation, Karen Elise Jensen Foundation.