1999 European Regional Conference Proceeding

May 12 - 16, 1999

Conference: 1999 European Regional Conference
Title: Mutations in the vasopressin V2 receptor and aquaporin-2 genes in twelve families with congenital nephrogenic diabetes insipidus
Authors: Vargas-Poussou, Rosa; Forestier, Lionel; Dautzenberg, Marie Dominique; Niaudet, Patrick; Dechaux, Michele; Antignac, Corinne
Institutions: Hopital Necker-Enfants Malades Tour Lavoisier, Hopital Necker Enfants Malades Tour Lavoisier, Institut National de la Sante' et de la Recherche Medicale, INSERM
Nine Knoers Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by renal tubular insensitivity to the antidiuretic effect of arginine vasopressin (AVP). In the large majority of the cases, NDI is an X-linked recessive disorder caused by mutations in the AVP V2 receptor gene (AVPR2). In the remaining cases, the disease is autosomal recessive or dominant and for these patients, mutations in the aquaporin 2 gene (AQP2) have been reported. We analyzed 16 probands belonging to 14 families by SSCP and direct sequencing of the AVPR2 and AQP2 genes. We identified 11 mutations of the AVPR2 gene: 7 previously reported mutations: Y205C, H80R, R337X, R202C, P322S, R113W and A147V; and 4 novel mutations: G107E, W193X, L43P, and 15delC. Three mutations of the AQP2 gene were also identified in two patients: the first patient is homozygous for the R85X mutation and the second is a compound heterozygote for V168M and S216P mutations. Extra-renal responses to infusion of the strong V2 agonist, 1-des-amino-8-D-arginine vasopressin (DDAVP), allowed us to distinguish V2R and AQP2 associated forms of CNDI in three patients. This test also allows us to identify an unexpectedly high urinary osmolality (614 mOsm/kg) in a patient with a P322S mutation of AVPR2 gene and a mild form of CNDI (ie diagnosed at 9 years of age, without previous episodes of hypernatremic dehydration).

Vargas-Poussou, et al., analyzed 16 congenital nephrogenic diabetes insipidus (CNDI) patients for mutations of either the vasopressin-2 (AVPR2) gene or the aquaporin-2 (AQP2) gene. The researchers identified 11 AVPR2 gene mutations, seven of which had been previously reported in the literature and four of which had not. Three AQP2 mutations were identified, two of which were found in the same NDI patient.

By administering a synthetically modified form of vasopressin called dDAVP, the researchers were able to distinguish the AVPR2- and AQP2-associated forms of CNDI in three patients. This test also identified a patient with a mild form of CNDI who had an unexpectedly high level of urine concentration.