Novel Mutations in the V2 Vasopressin Receptor Gene of Patients with X-Linked Nephrogenic Diabetes Insipidus
| Title: | Novel Mutations in the V2 Vasopressin Receptor Gene of Patients with X-Linked Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Wenkert, M.D., Ph.D., David; Merendino, Jr., John J.; Shenker, Andrew; Thambi, Nina; Robertson, Gary; Moses, Arnold M.; Spiegel, M.D., Allen M. |
| Publisher: | Human Molecular Genetics |
| Date Published: | August 01, 1994 |
| Reference Number: | 95 |
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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)
The V2R lives within the cell membrane, that porous band that separates the inside of the cell from the outside. If you think of the V2R as a long string, picture most of it sitting inside the cell membrane in seven distinct clumps called transmembrane helices. Part of the receptor snakes outside of the cell forming three curves called extracellular loops and part of the receptor snakes into the inside of the cell forming three curves called the intracellular loops. The head of the string is outside the cell and the tail of the string is inside. (Please refer to the schematic presentation of the V2R gene for a visual presentation.) Mutations can occur at any point along the V2R. Also, there are different types of mutations that can affect the V2R gene: missense, nonsense and frameshift, to name the most frequently occurring.
Wenkert, et al., examined the V2R genes of seven NDI patients and identified several new mutations. The V2R gene has three exons -- sequences that contain information for synthesizing its protein -- and two introns -- sequences that do not code for creating the protein. Wenkert, et al., found mutations in different places among the patients. Some had mutations in the second exon of the gene, others had their mutation in the sixth transmembrane helix and another had his mutation in the tail end of his V2R gene.
The first patient had a missense mutation, a type of mutation that changes a codon (a set of three bases-nucleotides -- positioned side-by-side) so that it creates a different set of amino acids than a non-mutated V2R gene would. Since amino acids are the building blocks of protein, and the V2R is a protein, using different building blocks will result in a slightly different structure of the protein than normal. In this case the codon TGG took the place of codon CGG which resulted in the amino acid Trp instead of Arg. Patients two and three also had a missense mutation. Theirs changed CGT to TCT, changing Arg202 to Cys. All three of these mutations had been reported in other NDI patients.
Three of the remaining four patients had missense mutations in the sixth transmembrane area of the receptor. Patient four had a change of codon TAT to TGT which produced the amino acid Cys instead of Tyr28O. This mutation had previously been reported in another, unrelated family. Patients five, six and seven each had a mutation that had never been previously reported.
Patient five had GCG where GTG should have been. This produced the amino acid Ala instead of Val277. Patient six had two new mutations: CTG to CCG which changed Leu29 to Pro, and a change of GGG to GAG, which produced Glu instead of Gly13. Patient seven had TGA instead of CGA, which produced a truncated V2R lacking part of its sequence.
Further research is needed to determine exactly how these mutations interfere with the V2R's ability to function.