A low-affinity vasopressin V2-receptor gene in a kindred with X-linked nephrogenic diabetes insipidus.

In this study, a mutation in vasopressin Type 2 receptor (V2R) in a patient with hereditary nephrogenic diabetes insipidus (NDI) has been identified and characterized. The sequencing of the V2R gene from the patient revealed that there was a missense mutation (TAT to TGT) resulting in the substitution of 205Tyr for Cys in the putative third extracellular domain. The expression analysis in COS cells showed that the binding affinity of the mutant receptor (KD = 19.8 nM) for arginine vasopressin was much lower than that of the wild-type receptor (KD = 1.8 nM) so that intracellular cAMP production stimulated by arginine vasopressin was impaired in cells with the mutant V2R. From these results, it was concluded that the single amino-acid substitution of V2R is responsible for this familial disease.

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Nephrogenic Diabetes Insipidus Due to a New Mutation of the Arginine Vasopressin V2 Receptor Gene in a Girl Presenting with Non-Accidental Injury

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329903600616 ◽

1999 ◽

Vol 36 (6) ◽

pp. 779-782 ◽

Cited By ~ 9

Author(s):

C. P. C. Seem ◽

J. F. B. Dossetor ◽

M. D. Penney

Keyword(s):

Diabetes Insipidus ◽

Arginine Vasopressin ◽

Nephrogenic Diabetes Insipidus ◽

Receptor Gene ◽

Accidental Injury ◽

New Mutation ◽

Vasopressin V2 Receptor ◽

V2 Receptor ◽

Non Accidental Injury ◽

V2 Receptor Gene

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Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus.

Journal of the American Society of Nephrology ◽

10.1681/asn.v8121855 ◽

1997 ◽

Vol 8 (12) ◽

pp. 1855-1862 ◽

Cited By ~ 2

Author(s):

R Vargas-Poussou ◽

L Forestier ◽

M D Dautzenberg ◽

P Niaudet ◽

M Déchaux ◽

...

Keyword(s):

Diabetes Insipidus ◽

Arginine Vasopressin ◽

Nephrogenic Diabetes Insipidus ◽

Direct Sequencing ◽

Receptor Gene ◽

Single Strand Conformational Polymorphism ◽

Aquaporin 2 ◽

Congenital Nephrogenic Diabetes Insipidus ◽

V2 Receptor ◽

Aqp2 Gene

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by renal tubular insensitivity to the antidiuretic effect of arginine vasopressin (AVP). In a large majority of the cases, nephrogenic diabetes insipidus 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. Fourteen probands belonging to 12 families were analyzed by single-strand conformational polymorphism and direct sequencing of the AVPR2 and AQP2 genes. Ten mutations of the AVPR2 gene (six previously reported mutations and four novel mutations: G107E, W193X, L43P, and 15delC) were identified. 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 V168 M and S216P mutations. Extrarenal responses to infusion of the strong V2 agonist 1-desamino-8-D-arginine vasopressin allowed AVPR2- and AQP2-associated forms of CNDI to be distinguished in three patients. This test also identified an unexpectedly high urinary osmolality (614 mosmol/kg) in a patient with a P322S mutation of AVPR2 gene and a mild form of CNDI.

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