J Clin Endocrinol Metab 2002 Jun 01;876:2694-700. doi: 10.1210/jcem.87.6.8617.

Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families.

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Mutations in the aquaporin-2 gene (AQP2), encoding the vasopressin-regulated water channel of the renal collecting duct, are responsible for the autosomal recessive or dominant forms of congenital nephrogenic diabetes insipidus. We describe two new families with normal hypotensive and coagulation responses following the administration of desamino-8-D-arginine AVP, a clinical suggestion of normal vasopressin-2 receptors. The patients were compound heterozygotes for point mutations at nucleotide position 170 (CAG to CCG; Q57P) and at position 299 (GGA to GTA; G100V) in exon 1 of the AQP2 gene. Expression of the G57P and G100V AQP2 proteins in Xenopus oocytes showed only 1.3-fold and 1.2-fold increase, respectively, in the water permeability in contrast to 8.0-fold increase in oocytes injected with wild-type cRNA. Immunoblots of oocyte lysate revealed the intensities of the 29-kDa bands were comparable among oocytes injected with wild-type and mutant cRNAs. Immunocytochemistry showed the plasma membrane was not stained in oocytes injected with cRNA of Q57P and of G100V. These results provide evidence that the Q57P and G100V mutations in congenital nephrogenic diabetes insipidus are attributable to the misrouting of AQP2.

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???displayArticle.link??? J Clin Endocrinol Metab


Species referenced: Xenopus
Genes referenced: aqp2 avp avpr2 itga2b.1
GO keywords: water channel activity [+]

???displayArticle.disOnts??? nephrogenic diabetes insipidus
???displayArticle.omims??? DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL; NDI2 [+]