Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter March 12, 2016

Novel AVPR2 mutation causing partial nephrogenic diabetes insipidus in a Japanese family

  • Sumie Yamashita EMAIL logo , Astuko Hata , Takeshi Usui , Hirotsugu Oda , Atsushi Hijikata , Tsuyoshi Shirai , Naoto Kaneko and Daisuke Hata

Abstract

Background: X-linked recessive congenital nephrogenic diabetes insipidus (NDI) is caused by mutations of the arginine vasopressin type 2 receptor gene (AVPR2). More than 200 mutations of the AVPR2 gene with complete NDI have been reported although only 15 mutations with partial NDI has been reported to date.

Methods: We herein report a Japanese kindred with partial NDI. The proband is an 8-year-old boy who was referred to our hospital for nocturnal enuresis. Water deprivation test and hypertonic saline test suggested partial renal antidiuretic hormone arginine vasopressin (AVP) resistance.

Results: Analysis of genomic DNA revealed a novel missense mutation (p.L161P) in the patient. The patient’s mother was heterozygous for the mutation. Three-dimensional (3-D) modeling study showed that L161P possibly destabilizes the transmembrane domain of the V2 receptor, resulting in its misfolding or mislocalization.

Conclusions: Distinguishing partial NDI from nocturnal enuresis is important. A clinical clue for diagnosis of partial NDI is an incompatibly high level of AVP despite normal serum osmolality.


Corresponding author: Sumie Yamashita, Kitano Hospital Tazuke Kofukai Medical Research Institute, Department of Pediatrics, Osaka, Japan, E-mail:

Acknowledgments

We thank the patient and his family for their participation.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: AH and TS were supported by The Platform for Drug Design, Informatics, and Structural Lifescience (PDIS) from The Japan Agency for Medical Research and Development (AMED).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, et al. Molecular cloning of the receptor for human antidiuretic hormone. Nature 1992;357:333–5.10.1038/357333a0Search in Google Scholar

2. Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, et al. Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 1994;264:92–5.10.1126/science.8140421Search in Google Scholar

3. Spanakis E, Milord E, Gragnoli C. AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. J Cell Physiol 2008;217:605–17.10.1002/jcp.21552Search in Google Scholar

4. Fujimoto M, Okada S, Kawashima Y, Nishimura R, Miyahara N, et al. Clinical overview of nephrogenic diabetes insipidus based on a nationwide survey in Japan. Yonago Acta Med 2014;57:85–91.Search in Google Scholar

5. Sadeghi H, Robertson GL, Bichet DG, Innamorati G, Birnbaumer M. Biochemical basis of partial nephrogenic diabetes insipidus phenotypes. Mol Endocrinol 1997;11:1806–13.10.1210/mend.11.12.0017Search in Google Scholar

6. Bockenhauer D, Carpentier E, Rochdi D, van’t Hoff W, Breton B, et al. Vasopressin type 2 receptor V88M mutation: molecular basis of partial and complete nephrogenic diabetes insipidus. Nephron Physiol 2010;114:1–10.10.1159/000245059Search in Google Scholar

7. Inaba S, Hatakeyama H, Taniguchi N, Miyamori I. The property of a novel v2 receptor mutant in a patient with nephrogenic diabetes insipidus. J Clin Endocrinol Metab 2001;86:381–5.10.1210/jcem.86.1.7165Search in Google Scholar

8. Chen CH, Chen WY, Liu HL, Liu TT, Tsou AP, et al. Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients. J Hum Genet 2002;47:66–73.10.1007/s100380200002Search in Google Scholar

9. Takahashi K, Makita N, Manaka K, Hisano M, Akioka Y, et al. V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists. J Biol Chem 2012;287:2099–106.10.1074/jbc.M111.268797Search in Google Scholar

10. Sahakitrungruang T, Tee MK, Rattanachartnarong N, Shotelersuk V, Suphapeetiporn K, et al. Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families. Horm Res Paediatr 2010;73:349–54.10.1159/000308167Search in Google Scholar

11. Szalai C, Triga D, zinner A. C112R, W323S, N317K mutations in the vasopressin V2 receptor gene in patients with nephrogenic diabete. Hum Mutat 1998;12:137–8.10.1002/(SICI)1098-1004(1998)12:2<137::AID-HUMU16>3.0.CO;2-JSearch in Google Scholar

12. Neocleous V, Skordis N, Shammas C, Efstathiou E, Mastroyiannopoulos NP, et al. Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: a case report and review of the literature. Metabolism 2012;61:922–30.10.1016/j.metabol.2012.01.005Search in Google Scholar PubMed

13. Wildin RS, Cogdell DE, Valadez V. AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus. Kidney Int 1998;54:1909–22.10.1046/j.1523-1755.1998.00214.xSearch in Google Scholar PubMed

14. Tajima T, Nakae J, Takekoshi Y, Takahashi Y, Yuri K, et al. Three novel AVPR2 mutations in three Japanese families with X-linked nephrogenic diabetes insipidus. Pediatr Res 1996;39:522–6.10.1203/00006450-199603000-00022Search in Google Scholar PubMed

15. Faerch M, Christensen JH, Corydon TJ, Kamperis K, de Zegher F, et al. Partial nephrogenic diabetes insipidus caused by a novel mutation in the AVPR2 gene. Clin Endocrinol 2008;68:395–403.10.1111/j.1365-2265.2007.03054.xSearch in Google Scholar PubMed

16. Ala Y, Morin D, Mouillac B, Sabatier N, Vargas R, et al. Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol 1998;9:1861–72.10.1681/ASN.V9101861Search in Google Scholar PubMed

17. Robertson GL, Mahr EA, Athar S, Sinha T. Development and clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma. J Clin Invest 1973;52:2340–52.10.1172/JCI107423Search in Google Scholar PubMed PubMed Central

18. Soding J, Biegert A, Lupas AN. The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res 2005;33:W244–8.10.1093/nar/gki408Search in Google Scholar PubMed PubMed Central

19. Hijikata A, Yura K, Noguti T. Go M. Revisiting gap locations in amino acid sequence alignments and a proposal for a method to improve them by introducing solvent accessibility. Proteins 2011;79:1868–77.10.1002/prot.23011Search in Google Scholar PubMed PubMed Central

20. Marti-Renom MA, Stuart AC, Fiser A, Sanchez R, Melo F, et al. Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 2000;29:291–325.10.1146/annurev.biophys.29.1.291Search in Google Scholar PubMed

21. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 1993;26:283–91.10.1107/S0021889892009944Search in Google Scholar

22. Nejsum LN, Christensen TM, Robben J H, Milligan G, Deen PM, et al. Novel mutation in the AVPR2 gene in a Danish male with nephrogenic diabetes insipidus caused by ER retention and subsequent lysosomal degradation of the mutant receptor. NDT Plus 2011;4:158–63.10.1093/ndtplus/sfr010Search in Google Scholar PubMed PubMed Central

23. Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol 2005;16:2836–46.10.1681/ASN.2005040371Search in Google Scholar PubMed

24. Hong CR, Kang HG, Choi HJ, Cho MH, Lee JW, et al. X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study. J Pediatr Endocrinol Metab 2014;27:93–9.10.1515/jpem-2013-0231Search in Google Scholar PubMed

25. Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, et al. Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Hum Genet 1994;55:278–86.Search in Google Scholar

26. Rochdi MD, Vargas GA, Carpentier E, Oligny-Longpré G, Chen S, et al. Functional characterization of vasopressin type 2 receptor substitutions (R137H/C/L) leading to nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis: implications for treatments. Mol Pharmacol 2010;77:836–45.10.1124/mol.109.061804Search in Google Scholar PubMed PubMed Central

27. Arthus MF, Lonergan M, Crumley MJ, Naumova AK, Morin D, et al. Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 2000;11:1044–54.10.1681/ASN.V1161044Search in Google Scholar PubMed

28. van Lieburg AF, Knoers NV, Monnens LA. Clinical presentation and follow-up of 30 patients with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 1999;10:1958–64.10.1681/ASN.V1091958Search in Google Scholar PubMed

29. Nomura Y, Onigata K, Nagashima T, Yutani S, Mochizuki H, et al. Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation. J Clin Endocrinol Metab 1997;82:3434–7.10.1210/jcem.82.10.4312Search in Google Scholar PubMed

30. Giri D, Hart R, Jones C, Ellis I, Ramakrishnan R. An unusual case of hereditary nephrogenic diabetes insipidus (HNDI) affecting mother and daughter. J Pediatr Endocrinol Metab 2016;1:93–6.10.1515/jpem-2015-0174Search in Google Scholar PubMed

Received: 2015-8-15
Accepted: 2015-12-30
Published Online: 2016-3-12
Published in Print: 2016-5-1

©2016 by De Gruyter

Downloaded on 29.3.2024 from https://www.degruyter.com/document/doi/10.1515/jpem-2015-0323/html
Scroll to top button