Original Article

A Novel Mutation in the Arginine Vasopressin Receptor 2 Gene Causing Congenital Nephrogenic Diabetes Insipidus

10.4274/jcrpe.0097

  • Aslı Celebi Tayfur
  • Tugce Karaduman
  • Merve Ozcan Turkmen
  • Dilara Sahin
  • Aysun Caltik Yılmaz
  • Bahar Buyukkaragoz
  • Ayse Derya Bulus
  • Hatice Mergen

Received Date: 05.04.2018 Accepted Date: 04.07.2018 J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub] PMID: 29991464

Objective:

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to the arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by the mutations in the AVPR2 gene. Our objective is to report a novel mutation in AVPR2 gene causing CNDI in a 6-year-old boy presenting with growth failure and dull normal cognitive functions.

Methods:

The proband was the third off-spring of non-consanguineous parents and had polyuria (4.3 L/day), polydipsia (5 L/day). The diagnosis of CNDI was established by a water-deprivation and desmopressin challenge test. The genetic studies were also carried out in mother, siblings and affected family members due to they also had excessive fluid intake and diuresis. All exons of AVPR2 gene for all participants were amplified and sequenced. Bioinformatics analysis for wild-type and mutant AVPR2 were obtained with Swiss-Model and UCSF Chimera 1.10.2.

Results:

A novel hemizygous missense mutation was identified at the position 80th in exon 2 (p.H80Y) of AVPR2 in the proband. The proband’s mother, maternal aunt and grandmother were heterozygous and maternal uncle was hemizygous for this mutation. According to bioinformatic analysis, this mutation leads to significiant conformational changes in protein structure.

Conclusion:

p.H80Y mutation can obviously cause inappropriate folding of the protein. Therefore, the pathway of water homeostasis via AVPR2 and AVP can be improper and it can be the reason of DI. We suggest that future functional investigations of the H80Y mutation may provide a basis for understanding the pathophysiology of the NDI.

Keywords: AVPR2, Congenital nephrogenic diabetes insipidus, Mutation