2004 Global Researcher Conference Proceeding
April 09 - 11, 2004
| Conference: | 2004 Global Researcher Conference |
|---|---|
| Title: | Clinical and genetic approaches to the diagnosis of congenital polyuro-polydipsic syndromes |
| Authors: | Arthus, Marie-Francoise; Lonergan, Michele; Fujiwara, T. Mary; Bichet, Daniel G. |
| Institutions: | Hopital du Sacre-Coeur de Montreal, Montreal General Hospital |
We continue to receive a large number of referrals for families with congenital polyuro-polydipsic syndromes, all well characterized by a lack of urinary osmolality response to dDAVP. Mutation analysis was done on 87 families not included in our previous studies (82 new families with X-linked nephrogenic diabetes insipidus (NDI) secondary to AVPR2 mutations, and 5 new families with autosomal dominant (3) or autosomal recessive NDI secondary to AQP2 mutations). This report describes the diversity of mutations observed in a total of 199 families with AVPR2 mutations and 18 families with AQP2 mutations.
Among the 82 new X-linked families, there were 62 different putative disease-causing mutations (22 missense, 5 nonsense, 15 deletion, 4 insertion, and 16 large deletion). Two families were bearing two different missense mutations on the same allele. Thirty-two mutations (16 missense, 1 nonsense, 11 deletion, 3 insertion, and 1 complex mutation) were novel mutations not previously described. The parental origin of a de novo mutation was identified or inferred to have occurred on the basis of mutation and haplotype analysis in 11 families. Complex congenital polyuro-polydipsic syndromes not included in this report were characterized by water, sodium, potassium, and calcium loss in the urine, and polyhydramnios prenatally, all clinical and biochemical characteristics suggesting a Bartter-like syndrome. Mutational and in vitro functional studies may lead to potential specific therapies. Large deletions, not including the coding regions of the AVPR2 or AQP2 genes, may lead to identification of sequence-specific regulatory proteins.
Arthus and Lonergan detail the different mutations responsible for NDI found in 217 NDI families. 199 of the families had AVPR2 mutations and 18 families had AQP2 mutations. Of the most recent 87 families added to this report, 82 had AVPR2 mutations and the remaining had AQP2 mutations. There were 65 different mutations of the AVPR2 gene in this latter group and 33 of them had not previously been documented. Two families had two different AVPR2 mutations on the same allele. In addition, the researchers identified the parental origin of the “de novo” mutations found in 11 families.