Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

Abstract

Loss of function of arginine vasopressin receptor 2 (AVPR2) may affect the recognition and binding of arginine vasopressin (AVP) which, in turn, may prevent the activation of Gs/adenylate cyclase and reduce the reabsorption of water by renal tubules and combined tubes. Finally, the organism may suffer from nephrogenic diabetes insipidus (NDI), a kind of kidney disorder featured by polyuria and polydipsia, due to a break of water homeostasis. In this study, we enrolled a Chinese family with polyuria and polydipsia. The proband presented abnormal fluid intake and excessive urine output. A water deprivation and AVP stimulation test further indicated that this patient had NDI. By sequencing known causative genes for diabetes insipidus, we identified a novel mutation in AVPR2 (c.547G>A; p.V183M) in the family. This mutation, located in a conserved site of AVPR2 and predicted to be disease-causing by informatics programs, was absent in our 200 controls and other public databases. Our study not only further confirms the clinical diagnosis, but also expands the spectrum of AVPR2 mutations and contributes to genetic diagnosis and counseling of patients with NDI.

Keywords: Arginine vasopressin receptor 2; Nephrogenic diabetes insipidus; Novel mutation.

Fig. 1

a Pedigree of the family affected with X-linked dominant inherited NDI. Family members are identified by generations and numbers. Squares indicate male family members; circles, female members; black symbols, the affected members; open symbols, unaffected members; half black, the heterozygous carriers; arrow, proband. b Sequencing results of the AVPR2 mutation. Sequence chromatograms indicate a G to A transition of nucleotide 547. c Analysis of the mutation and protein domains of AVPR2 and alignment of multiple AVPR2 protein sequences across species. The affected amino acid V183 is located in the highly conserved amino acid region in different mammals (from Ensembl). Red letters show the V183 site.