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Kim, Lee, Jeong, Kang, Lee, Hong, Kim, Kim, Yoo, Ihm, Choi, and Yoo: A Novel Mutation of the Vasopressin-Neurophysin II Gene in a Familial Neurohypophyseal Diabetes Insipidus
Case Report
Journal of Korean Endocrine Society

Journal of Korean Endocrine Society 2007; 22(2): 118-124.

Published online: 20 April 2007

DOI: https://doi.org/10.3803/jkes.2007.22.2.118

A Novel Mutation of the Vasopressin-Neurophysin II Gene in a Familial Neurohypophyseal Diabetes Insipidus

Mi Jung Kim, Byung Wan Lee, In Kyung Jeong1, Jun Goo Kang, Seong Jin Lee, Eun Gyung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo

Department of Internal Medicine, Hallym University School of Medicine, Korea.

1Department of Internal Medicine, KyungHee University College of Medicine, Korea.

Received 27 October 2006       Accepted 13 November 2006

Copyright © 2007 Korean Endocrine Society

Abstract

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare form of central diabetes insipidus (DI), and this malady is clinically characterized by polydipsia and polyuria, and it is caused by mutation in the vasopressin-neurophysin II. We identified a Korean family that suffered with adFNDI and we found a novel mutation in the NP II molecule.
The index subject's DI symptoms dated to childhood, and his familial history was consistent with autosomal transmission. The diagnosis of central DI was done by performing a water deprivation test and a vasopressin challenge test. For molecular analysis, the genomic DNA was extracted and the AVP-NP II gene was amplified by polymerase chain reaction from four clinically-affected members and seven clinically-nonaffected members. Genetic analysis of AVP-NP II revealed new a heterozygous missense mutation in exon 2 of the AVP-NP II gene (+1692C > A) and this amino acid substitution (Cys105Stop) was predicted to have occurred in four clinically-affected subjects.
In summary, in the present study we have described a novel mutation of the AVP-NPII gene in a Korean family suffering with adFNDI.

Keywords: Central diabetes insipidus, Korean Family, Vasopressin-neurophysin II

Figures and Tables

Fig. 1
The pedigree of the Korean family with adFNDI.
Grey symbols depict members who were clinically affected (polydipsia and polyuria) but not gene tested; blackened symbols depict mutant gene-positive members who were clinically affected; open symbols depict clinically nonaffected members.
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Fig. 2
Sellar MRI.
Sellar MRI shows the loss of high signal intensity on posterior pituitary gland.
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Fig. 3
Automated sequencing of the AVP-NP II gene.
A portion of exon 2 of AVP-NP II gene, in which the novel mutation was identified, is represented. The box shows a mutation from C to A at the position of 1692 in the affected persons.
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Fig. 4
Schematic diagram of the AVP gene.
SP, signal peptide; VP, arginine vasopressin; NP, neurophysin II; CP, copeptin.
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Fig. 5
Schematic diagram representing NP II gene with one +3692 C > A substitution mutation and five SNPs (1935G > A, 1215A > G, 100T > C, +373A > G and +1211C > C) on 20p13 (2.87 Kb).
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Table 1
Water deprivation test
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*Arginine vasopressin 5U injection.

Table 2
Results of the plasma & urine osmolality of symptomatic subjects (number 13 and 9)
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Table 3
Primers sequence of NP II gene
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