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A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus
J Clin Res Pediatr Endocrinol. 2018 11 29; 10(4):350-356.JC

Abstract

Objective

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a novel mutation in the 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 test and a desmopressin challenge test. Genetic studies were also carried out in the mother, siblings and affected family members, since excessive fluid intake and diuresis were also reported in these individuals. All exons of the 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 his maternal uncle was hemizygous for this mutation. Bioinformatic analysis indicates this mutation would cause significant conformational changes in protein structure.

Conclusion

p.H80Y mutation will cause inappropriate folding of the protein compromising water homeostasis via AVPR2 and AVP and leading to diabetes insipidus. We suggest that future functional investigations of the H80Y mutation may provide a basis for understanding the pathophysiology of the NDI in patients with this variant.

Authors+Show Affiliations

Keçiören Training and Research Hospital, Clinic of Pediatric Nephrology, Ankara, TurkeyHacettepe University Faculty of Science, Department of Biology, Ankara, TurkeyHacettepe University Faculty of Science, Department of Biology, Ankara, TurkeyHacettepe University Faculty of Science, Department of Biology, Ankara, TurkeyKeçiören Training and Research Hospital, Clinic of Pediatric Nephrology, Ankara, TurkeyKeçiören Training and Research Hospital, Clinic of Pediatric Nephrology, Ankara, TurkeyKeçiören Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, TurkeyHacettepe University Faculty of Science, Department of Biology, Ankara, Turkey

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

29991464

Citation

Çelebi Tayfur, Aslı, et al. "A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus." Journal of Clinical Research in Pediatric Endocrinology, vol. 10, no. 4, 2018, pp. 350-356.
Çelebi Tayfur A, Karaduman T, Özcan Türkmen M, et al. A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus. J Clin Res Pediatr Endocrinol. 2018;10(4):350-356.
Çelebi Tayfur, A., Karaduman, T., Özcan Türkmen, M., Şahin, D., Çaltık Yılmaz, A., Büyükkaragöz, B., Buluş, A. D., & Mergen, H. (2018). A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus. Journal of Clinical Research in Pediatric Endocrinology, 10(4), 350-356. https://doi.org/10.4274/jcrpe.0097
Çelebi Tayfur A, et al. A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus. J Clin Res Pediatr Endocrinol. 2018 11 29;10(4):350-356. PubMed PMID: 29991464.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus AU - Çelebi Tayfur,Aslı, AU - Karaduman,Tuğçe, AU - Özcan Türkmen,Merve, AU - Şahin,Dilara, AU - Çaltık Yılmaz,Aysun, AU - Büyükkaragöz,Bahar, AU - Buluş,Ayşe Derya, AU - Mergen,Hatice, Y1 - 2018/07/11/ PY - 2018/7/12/entrez PY - 2018/7/12/pubmed PY - 2019/2/8/medline KW - AVPR2 KW - congenital nephrogenic diabetes insipidus KW - mutation SP - 350 EP - 356 JF - Journal of clinical research in pediatric endocrinology JO - J Clin Res Pediatr Endocrinol VL - 10 IS - 4 N2 - Objective: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a novel mutation in the 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 test and a desmopressin challenge test. Genetic studies were also carried out in the mother, siblings and affected family members, since excessive fluid intake and diuresis were also reported in these individuals. All exons of the 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 his maternal uncle was hemizygous for this mutation. Bioinformatic analysis indicates this mutation would cause significant conformational changes in protein structure. Conclusion: p.H80Y mutation will cause inappropriate folding of the protein compromising water homeostasis via AVPR2 and AVP and leading to diabetes insipidus. We suggest that future functional investigations of the H80Y mutation may provide a basis for understanding the pathophysiology of the NDI in patients with this variant. SN - 1308-5735 UR - https://www.unboundmedicine.com/medline/citation/29991464/A_Novel_Mutation_in_the_AVPR2_Gene_Causing_Congenital_Nephrogenic_Diabetes_Insipidus L2 - https://doi.org/10.4274/jcrpe.0097 DB - PRIME DP - Unbound Medicine ER -