Mutations in the Vasopressin V2-Receptor Gene in Three Families of Italian Descent with Nephrogenic Diabetes Insipidus

Title: Mutations in the Vasopressin V2-Receptor Gene in Three Families of Italian Descent with Nephrogenic Diabetes Insipidus
Authors: Faa, V.; Ventruto, M. L.; Loche, S.; Bozzola, M.; Podda, R.; Cao, A.; Rosatelli, M.C.
Publisher: Human Molecular Genetics
Date Published: September 01, 1994
Reference Number: 90

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 vast majority of cases of congenital NDI are inherited in an X-linked recessive manner. Researchers have identified mutations of the vasopressin-2 receptor (V2R) gene as the molecular basis for this form of NDI. Mutations of the V2R gene result in structural abnormalities in the V2Rs the genes produce, and these structural alterations affect the V2Rs' ability to function. Researchers study the structure-function relationship of the V2R to better understand the V2R and its role in the urine concentrating process and to try to find effective therapeutic approaches to NDI.

Faa, et al., report on the mutations of the V2R gene in three male NDI patients of Italian descent. Two of the patients had what is called a point-mutation. This type of mutation results from a change in a single base pair in the V2R gene caused by the substitution of one nucleotide for another. This results in the V2R gene producing a different amino acid than normal at the site of the point mutation. Since amino acids are the building blocks of protein, and V2R is a protein, this will result in a structural change in the V2R.

In one patient's V2R gene there was an A to C mutation at nucleotide position 454. (Genes are strings of nucleotide bases linked by sugar and phosphate side chains. There are four types of base: adenine (A), cytosine (C), guanine(G), and thymine (T).) This resulted in the amino acid, tyrosine forming instead of serine. This mutation has been found in other NDI patients.

The other patients point mutation was a C to T mutation at nucleotide position 928 leading to a proline amino acid substitution for a leucine amino acid. The third patient's V2R gene mutation resulted from a deletion of a single set of three nucleotide bases (a codon), specifically codon 279. The latter two mutations had never been previously reported in the literature.