DISEASE OF THE MONTH Congenital Nephrogenic Diabetes Insipidus

Congenital nephrogenic diabetes insipidus (NDI) is a rare disorder of the kidney characterized by the failure to concen-trate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine vasopressin (AVP). The identifica-tion, characterization, and mutational analysis of two different genes, i.e., the AVP receptor 2 gene (AVPR2) and the vasopressin-sensitive water channel gene (aquaporin-2 [AQP2]), provide the basis for our understanding of two different hereditary forms of ND!: X-linked ND! and autosomal recessive NDI. A majority (>90%) of congenital ND! patients have AVPR2 mutations: Of 1 15 families with congenital ND! that were referred to our labo-ratories in Montreal and Berlin, 105 families had A VPR2 muta-tions and 10 had AQP2 mutations. When studied in vitro, most AVPR2 mutations lead to receptors that are trapped intracellularly and are unable to reach the plasma membrane. A minority of th