Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families.Horm Res Paediatr. 2010; 73(5):349-54.HR
AVPR2 mutations cause most cases of nephrogenic diabetes insipidus (NDI); 211 AVPR2 mutations have been described, but only 7 are described causing partial NDI.
Two unrelated Thai boys had polyuria and polydipsia in infancy but had normal electrolytes and serum osmolality at 2 years of age. Patient 1 could not concentrate his urine in response to water deprivation or 1-desamino-8-D-arginine vasopressin (DDAVP); patient 2 could concentrate to approximately 600 mosm/l. The patients' AVPR2 genes were sequenced and the identified mutations were re-created in AVPR2 cDNA expression vectors. AVPR2 activities were measured by stimulating transfected HEK293T cells with arginine vasopressin (AVP) or DDAVP, and assessing the resulting cAMP production by the activation of a luciferase reporter.
Patient 1 carried the previously described missense mutation R181C; patient 2 carried the novel missense mutation M311V. When transiently transfected into HEK293T cells, 6.8 x 10(-12) M AVP induced the half-maximal response (EC50) of the wild-type, whereas the EC50 value for R181C was 5.9 x 10(-9) M and for M311V was 2.6 x 10(-10)M. Responses to DDAVP were qualitatively similar but required 10-fold higher concentrations.
The novel AVPR2 mutation M311V retains partial activity and results in a milder form of NDI.