Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype.

X-linked nephrogenic diabetes insiDidus (NDI) is a rare disease with defective renal and extrarenal arginine vaso- pressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. To study the cause of loss of function of mutant V2 receptors, we expressed 12 mutations (N5SH, L59P, L83Q, V88M, 497CC -� GG, zR202, 1209F, 700delC, 9O8insT, A294P, P322H, P3225) in COS-7 cells. Eleven of these, in- cluding P322H, were characterized by a complete loss of function, but the mutation P322S demonstrated a mild clinical and in vitro phenotype. This was characterized by a late diag- nosis without any growth or developmental delay and a sig- nificant increase in urine osmolality after intravenous 1-deami-