Novel vasopressin type 2 (AVPR2) gene mutations in Brazilian kindreds with nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus (NDI) is an inherited disorder characterized by renal resistance to the antidiuretic effect of arginine vasopressin (AVP), resulting in polyuria, polydipsia and hypoosmolar urine. It the vast majority of cases, NDI is associated with germline mutations in the vasopressin receptor type 2 gene (AVPR2) and in about 8% of the cases with the water channel aquaporin-2 gene (AQP-2) gene mutations. To date, approximately 277 families with 185 germline mutations in the AVPR2 gene have been described worldwide. In the present study the AVPR2 gene was genotyped in eight unrelated Brazilian kindred with NDI. In five NDI families novel mutations were noted (S54R, I130L, S187R, 219delT, and R230P) whereas three seemingly unrelated probands were found to harbor previously described AVPR2 gene mutations (R106C, R137H, R337X). Additionally a novel polymorphism (V281) was detected. In conclusion, although NDI is a rare disease, the findings of mutations scattered over the entire coding region of the AVPR2 gene are a valuable model to determine structure function relationship in G protein-coupled receptor related diseases. Furthermore, our data indicate that in Brazil the spectrum of AVPR2 gene mutations is "family specific”.
This work was made possible by grants from CNPq, CAPES and FAPEMIG (Brasil).