Analysis of vasopressin receptor type II (V2R) gene in three Japanese pedigrees with congenital nephrogenic diabetes insipidus: identification of a family with complete deletion of the V2R gene

Abstract

To investigate the association of mutations in the arginine vasopressin receptor type II (V2R) gene with congenital nephrogenic diabetes insipidus (CNDI) in the Japanese, we analyzed the V2R gene, located on the X chromosome, in three Japanese pedigrees with CNDI. In one pedigree, a large deletion spanning the entire coding region of the V2R gene was identified. In another pedigree, a G to A transition responsible for a substitution of Met88 (ATG) for Val88 (GTG) was detected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis revealed that this was a de novo mutation that had occurred in the proband's mother. Because CNDI was observed only in those with this mutation, the pathogenicity of this mutation seemed clear. In the last pedigree, only a silent mutation at Leu309 (CTA-->CTG) was found. All the individuals studied in this pedigree by allele-specific oligonucloetide-polymerase chain reaction (ASO-PCR) analysis showed a complete association of this mutation to the clinical symptoms. Because the silent mutation detected was unlikely to be a direct cause of CNDI, mutations in other regions of the V2R gene, such as a promoter region or other regulatory regions, may be responsible for the cause of CNDI in this pedigree. Thus, association of the V2R gene abnormality to clinical symptoms of CNDI was confirmed in three Japanese pedigrees, and a strong contribution of the V2R gene mutation to the development of CNDI was suggested.

Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus

“…Very few cases of NDI caused by submicroscopic deletions or rearrangements have been reported [ Bichet et al, 1994;Jinnouchi et al, 1996;Schoneberg et al, 1999;Arthus et al, 2000]. However, precise identification of the breakpoints was only done in one report [Schoneberg et al, 1999].…”

“…However, there are a small number of reports describing the total deletion of the AVPR2 gene [Bichet et al, 1994;Jinnouchi et al, 1996;Schoneberg et al, 1999;Arthus et al, 2000].…”

Diversity of nephrogenic diabetes insipidus mutations and importance of early recognition and treatment

“…Arginine vasopressin activates adenylate cyclase increasing the intracellular concentration of cyclic adenosine monophosphate (cAMP). The topology of adenylyl cyclase TM,: L43P [3], L44F [4], L44P [5], L53R [6] C~: L62P [4] TM,,: H80R [3,7], L83P [6], 985N [4,8], V88M [4,9,10], P95L [6] E~,: R106C [9], G107E [3] TM~,: Cl12R [9], R113W [4,[11][12][13], S126F [9], Y128S [9,14,15] C,: A132D [16], R137H [9,11,17], R143P [18], A147V [3,9] TM~v: W164S [9], $167L [4,6,9], S167T [5] E,,,: R181C [4,9,14], G185C [19], R202C [3,9,13,19,20], T204N [4], Y205C [3,6,…”

Development of a High-Sensitivity Quantitation Method for Arginine Vasopressin by High-Performance Liquid Chromatography Tandem Mass Spectrometry, and Comparison with Quantitative Values by Radioimmunoassay

“…The second-most common type of diabetes insipidus is nephrogenic diabetes insipidus, which is due to kidney or nephron dysfunction caused by an insensitivity of the kidneys or nephrons to AVP. 3,4 Furthermore, AVP causes the vasoconstriction of peripheral blood vessels, which leads to increased arterial pressure. 5,6 In contrast, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is caused by over-secretion of AVP.…”