Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus.

Families with congenital nephrogenic diabetes insipidus were analyzed with regard to mutations in the vasopressin V2 receptor gene. Family 1 shows an X-chromosomal recessive inheritance of the disease over 4 generations. A patient from this family was found to have a T-->A transversion at nucleotide 1095, predictive for a substitution of serine 167 (which is highly conserved among G-protein-coupled receptors), by threonine. Both the mutant and the normal allele were detected in the maternal genome. The patient's healthy brother was homozygous for the normal allele. The patient from family 2 showed a T-->C transition at nucleotide 727, predictive for a substitution of leucine 44 by proline. Analysis of the maternal genome revealed homozygosity for the normal allele. Thus a de novo mutation seems to have occurred. The nature and site of the mutation in family 2 suggest that it is responsible for the patient's disease.