Molecular Analyses of the Vasopressin Type 2 Receptor and Aquaporin-2 Genes in Brazilian Kindreds with Nephrogenic Diabetes Insipidus
| Title: | Molecular Analyses of the Vasopressin Type 2 Receptor and Aquaporin-2 Genes in Brazilian Kindreds with Nephrogenic Diabetes Insipidus |
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| Authors: | Rocha, Juliane L.; Friedman, Eitan; Boson, Wolfanga L.; Moreira, A.C.; Figueiredo, Bonald; Liberman, Bernardo; de Lacerda, Luiz; Sandrini, Romulo; Graf, Hans; Martins, Sonia; Punales, Marcia K.; De Marco, Luiz |
| Publisher: | Human Mutation |
| Date Published: | 1999 |
| Reference Number: | 492 |
Nephrogenic diabetes insipidus (NDI) is associated with germline mutations in two genes: vasopressin receptor type 2 (V2(R)) in X-linked NDI, and the water channel aquaporin-2, in autosomal-recessive disease. Genetic heterogeneity is further emphasized by reports of phenotypically abnormal individuals with normal structural genes. We analyzed both genes in five Brazilian families and the aquaporin-2 gene in two Swedish families with clinical and laboratory diagnosis of NDI, by a combination of denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing. A novel polymorphism in the aquaporin-2 gene (S167S), but no disease-associated mutations in any tested individual from all seven families, was detected. In two Brazilian families, frameshift mutations were detected in the V2(R) gene: one leading to a premature stop after codon 36 and the other to a longer peptide (462 aa instead of the 373 aa wild-type protein). In two other Brazilian families, probable disease-associated missense mutations were detected: an alanine to proline at codon 163 (A163P) and an asparagine to aspartic acid at codon 85 (D85N). In one Brazilian family, both genes were structurally normal and the aquaporin-2 gene was also normal in the two Swedish kindreds. This report further extends the mutational spectrum of NDI and suggests that there are other mutational or epigenetic events inactivating the two known genes or even novel genes that underlie NDI.
Copyright 1999 Wiley-Liss, Inc.
Copyright 1999 Wiley-Liss, Inc.
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)
The researchers found a total of five V2R gene mutations among four of the Brazilian families. In the remaining Brazilian family, the NDI patients' had structurally normal V2R and AQP2 genes. The AQP2 gene was normal in the two Swedish families. Thus, the research suggests that there may be other genes that, when mutated, result in NDI. The authors also state that there may be phenomena that alter the activity of the AQP2 and V2R genes without changing their structure.