2000 Global Researcher Conference Proceeding
March 10 - 12, 2000
| Conference: | 2000 Global Researcher Conference |
|---|---|
| Title: | Two new Aquaporin-2 mutations responsible for Congenital Nephrogenic Diabetes Insipidus |
| Authors: | Lin, Shih-Hua; Lin, Yuh-Feng; Arthus, Marie-Francoise; Lonergan, Michele; Bichet, Daniel G. |
| Institutions: | Tri-Service General Hospital, Hopital du Sacre-Coeur de Montreal |
Nephrogenic diabetes insipidus (NDI) which can be inherited or acquired is characterized by the failure to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine-vasopressin. About 90% of patients with congenital NDI are males with X-linked recessive NDI and have mutations in the AVPR2 gene that codes for the vasopressin V2 receptor which is located in chromosome region Xq28. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance and mutations have been identified in the aquaporin-2 gene (AQP2) located in chromosome region 12q13, that codes for the vasopressin-sensitive water channel. We describe two new families with congenital NDI and normal hypotensive and coagulation responses following the administration of dDAVP, a clinical suggestion of normal V2 receptors. These two families, although unrelated, were found to be compound heterozygotes for the same two new mutations G100V and Q57P. Haplotype analysis revealed that the alleles bearing each individual mutation were identical, a suggestion of a single origin for each mutated allele. The identification of these mutations will be useful for future perinatal diagnosis if the frequency of the mutated allele is high in the population studied.
The vast majority of cases of congenital NDI are due to mutations of the vasopressin-2 receptor (AVPR2) gene. A minority are due to mutations of the aquaporin-2 (AQP2) gene. Lin, et al., describe two unrelated families with congenital NDI, the NDI patients of which demonstrate normal AVPR2 but abnormal AQP2 function. These families each carry the same two new AQP2 mutations, G100V and Q57P. Genetic analysis of both families revealed that the genes bearing each individual mutation were identical. This suggests a single origin for each mutated gene. Knowledge of these two mutations will help clinicians in their diagnosis of congenital NDI.