1999 European Regional Conference Proceeding
May 12 - 16, 1999
| Conference: | 1999 European Regional Conference |
|---|---|
| Title: | Complete deletions of the vasopressin type 2 receptor gene in nephrogenic diabetes insipidus |
| Authors: | Hoefsloot, Lies H.; Verdijk, Marian A.J.; Schoute, Frans; Ligtenberg, Marjolijn J.L.; Knoers, Nine |
| Institutions: | University Medical Centre Nijmegen, University Hospital Nijmegen |
Nephrogenic diabetes insipidus (NDI) is due to a concentration defect of the kidney, caused by a renal insensitivity to the antidiuretic effect of arginine vasopressin. In 90% of the cases, a mutation is found in the vasopressin type-2 receptor gene (AVPR2), localized on the X-chromosome. The remaining cases are inherited in an autosomal recessive and dominant fashion, and in these cases, mutations in the aquaporin-2 (AQ2) water channel gene have been found.
The AVPR2-gene has been studied intensively, and many putative disease-causing mutations have been found, including point mutations, small insertions and deletions, and splice site mutations. Large deletions have been reported for the 3'end, and for the total gene in one Japanese case.
Here we report the analysis of five families in which a deletion of the AVPR2-gene has been found. Southern blot analyses with probes of the V2-receptor region in combination with PCR assays using primer pairs that amplify the AVPR2-gene were used. We found that one family had a deletion of the 5'end of the gene that cosegregated with the disease. The other four families had a complete deletion of the AVPR2-gene. Two of these were sporadic cases, and in one of the other families, cosegregation with the disease could be shown.
These data indicate that a significant part of mutations found in the AVPR2-gene is caused by a deletion of the coding sequence.
Nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to reabsorb water flowing through its collecting ducts in response to the antidiuretic hormone, arginine vasopressin (AVP). Ninety percent of all the cases of congenital NDI are due to mutations of the vasopressin-2 receptor (AVPR2) gene, which is carried on the X-chromosome. The remaining 10% are due to mutations of the aquaporin-2 (AQP2) gene, which is carried on chromosome 12.
There are many different types of AVPR2 mutations. Hoefsloot and Knoers, et al., analyzed five families who had members with NDI. These NDI carriers and patients had deletion mutations of their AVPR2 genes. A deletion mutation occurs when a portion or all of the gene is absent. The researchers found that one NDI family had a section of their AVPR2 gene called the 5'end missing. And the NDI members and carriers of the other four families had a total deletion of the AVPR2 gene. This analysis indicates that a significant portion of the mutations in the AVPR2 gene are deletion mutations where the coding sequence of the gene is absent.