A NOVEL INTRAGENIC DELETION RELATED TO THE ARGININE VASOPRESSIN V2 RECEPTOR CAUSES NEPHROGENIC DIABETES INSIPIDUS

Abstract

Background: Nephrogenic diabetes insipidus (NDI) is a disease characterized by a defective response to the antidiuretic hormone (ADH) of the renal collecting duct leading to a decline in the ability of the pro-urine concentration.

Case presentation: A 23-year-old man presented with an over 20-year history of polyuria concomitant with hydronephrosis. The diagnosis of NDI was established by gene analysis as well as a water-deprivation and vasopressin test. All exons of arginine vasopressin V2 receptor (AVPR2) gene were amplified and sequenced. A novel hemizygous intragenic inframe deletion, cDNA 255^th bp to 263^th bp in exon 2 of AVPR2, was identified. These relevant translations from the 85^th amino acid Asp to 88^th amino acid Val were missed and replaced by amino acid Glu. After treating the patient with hydrochlorothiazide, his symptoms improved significantly.

Conclusion: The genetic analysis revealed a novel X-linked intragenic inframe deletion, AVPR2 gene cDNA 255^th bp to 263^th bp, causing NDI.

Keywords: Nephrogenic diabetes insipidus; arginine vasopressin V2 receptor; intragenic inframe deletion; polyuria.

Figure 1.

The images of the patient with NDI and the comparison of the base sequences between the normal AVPR2 gene and the AVPR2 gene with the intragenic inframe deletion. Notes: A) To reduce the impact of the large output of nocturnal urine interfering the patient’s rest, a bladder fistula was placed in his lower abdomen; B) CT scan indicated hydronephrosis; C) A sagittal MRI image showed that the feature of pituitary was hyperintensity in this patient with NDI, which was totally different from hypointensity of pituitary in CDI; D a) Normal base sequences for AVPR2 gene ranging from 253^th to 264^th are -GACCTGGCCGTG-; D b) The intragenic inframe deletion of AVPR2 with half-zygote was detected: c.255_263del9. The relevant translated protein from the 85^th amino acid Asp to 88^th amino acid Val was lost, and it is replaced by the amino acid Glu, d. (Asp85_Val88 delinsGlu).