Journal List > J Korean Endocr Soc > v.22(2) > 1003351

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


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.

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.
Fig. 2
Sellar MRI.
Sellar MRI shows the loss of high signal intensity on posterior pituitary gland.
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.
Fig. 4
Schematic diagram of the AVP gene.
SP, signal peptide; VP, arginine vasopressin; NP, neurophysin II; CP, copeptin.
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).
Table 1
Water deprivation test

*Arginine vasopressin 5U injection.

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


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