Six Novel Mutations in the Vasopressin V2 Receptor Gene Causing Nephrogenic Diabetes Insipidus
| Title: | Six Novel Mutations in the Vasopressin V2 Receptor Gene Causing Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Cheong, Hae Il; Park, Hye Won; Ha, Il Soo; Moon, Hyung Nam; Choi, Yong; Ko, Kwang Wook; Jun, Jong Kwan |
| Publisher: | Nephron |
| Date Published: | 1997 |
| Reference Number: | 175 |
X-linked nephrogenic diabetes insipidus (NDI) is a rare disease caused by mutations in the vasopressin V2 receptor (AVPR2) gene. We analyzed the AVPR2 gene in 6 unrelated Korean families with X-linked NDI, and found 6 novel mutations. Two of them were missense point mutations, 2 were short deletions causing frameshifts, 1 was a duplication of 9 bases, and 1 was a compound gene rearrangement. Four mutations cosegregated with the clinical phenotype in corresponding family members, and one was a de novo mutation. In 1 family, prenatal diagnosis was made by amniocentesis. In conclusion, we found 6 novel mutations in the AVPR2 gene causing X-linked NDI in 6 families, and direct mutational analysis is now applicable for carrier detection and early (prenatal) diagnosis.
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)
A gene is a complex organism with many parts and any change in its genetic material can result in the gene producing a defective protein. Over 63 distinct mutations of the AVPR2 gene have been reported worldwide. There have been different types of mutations located on different parts of the AVPR2 gene, but they have all resulted in defective AVPR2s incapable of responding to AVP.
Cheong, et al., analyzed the AVPR2 gene in six unrelated Korean families with X-linked NDI and found six mutations that have never been reported in the literature. Two of the mutations were missense point mutations. Each gene has a sequence of four simple chemicals called nucleotide bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The cell reads the bases in units of three (e.g. CGG or ATC or AGT, etc.). Each of these triplets of bases, called a codon, codes for a specific amino acid. In a missense mutation, there is a change of codon in the gene so it codes for a different amino acid than needed.
The authors found two other mutations that were frameshift mutations. Frameshift mutations are due to an addition or deletion in the gene's coding sequence in which the cell reads the codons out of phase resulting in the gene making a protein out of a completely different set of amino acids. The fifth mutation they found involved a duplication of nine bases. And the final mutation was a compound gene rearrangement.
In one family, the authors analyzed the patient while he was still in utero by analyzing a sample of amniotic fluid. The authors state that prenatal or immediate postnatal diagnosis of an infant can prepare parents, doctors and caregivers to treat for NDI (if it is detected) immediately and possibly avert complications that can arise from NDI.