Novel Vasopressin Type 2 (AVPR2) Gene Mutations in Brazilian Nephrogenic Diabetes Insipidus Patients

Title: Novel Vasopressin Type 2 (AVPR2) Gene Mutations in Brazilian Nephrogenic Diabetes Insipidus Patients
Authors: Boson, Wolfanga L.; Manna, T. Della; Damiani, D.; Miranda, D. M.; Gadelha, M.R.; Liberman, Bernardo; Correa, H.; Romano-Silva, M.A.; Friedman, Eitan; Silva, F.F.; Ribeiro, P.A.; De Marco, M.D., Ph.D., L.
Publisher: Genetic Testing
Date Published: September 01, 2006
Reference Number: 713

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. In the vast majority of cases, NDI is associated with germ-line 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) mutations. To date, approximately 277 families with 185 germ-line 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 of these 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 (V281V) 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".

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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Boson, et al., note that researchers worldwide have found 188 different mutations of the vasopressin-2 receptor (V2R) gene that result in NDI. In their study, Boson, et al., examined eight different Brazilian families and their kindred that evidenced NDI. The researchers discovered that each of five of these families had a V2R gene mutation that had not been previously discovered by science. The other three families each had a V2R gene mutations that had previously been described by scientists. The five novel mutations were: S54R, I130L, S187R, 219delT and R230P. The three mutations previously found by researchers were: R106C, R137H, R337X. The researchers also detected a novel polymorphism (V281V).

Boson, et al., noted that the V2R mutations they found in their NDI families were scattered over the entire coding region of the V2R gene. Most of them, however, came from the section of the gene known as exon two. The researchers described the value of examining the structure-function relationship of the mutations, pointing out that knowledge of the structure of the mutation can present an idea of how the mutant V2R will carry out its function, if at all. For instance, in a normal V2R the serine (S) amino acid is the 54th amino acid in the chain of amino acid residues that is the V2R. In the S54R mutations, that serine is replaced with an arginine (R) amino acid. S is a small, neutral amino acid that readily absorbs water. R is basic and positively charged. Replacing the neutral S with the charged R can be expected to disrupt the proper assembly of the V2R. The researchers state that some mutations will alter the structure of the V2R protein, and hence alter the ability for it to function, more than others. This will affect the severity of NDI symptoms experienced.