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

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


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:


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.


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

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