Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus

Tian,Dan; Cen,Jing; Nie,Min; Gu,Feng

doi:10.3892/ijmm.2016.2703

Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus

Authors:
- Dan Tian
- Jing Cen
- Min Nie
- Feng Gu
View Affiliations

Affiliations: Department of Nuclear Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China, Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
Published online on: August 11, 2016 https://doi.org/10.3892/ijmm.2016.2703
Pages: 1243-1249

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Familial neurohypophyseal diabetes insipidus (FNDI) is a genetic disorder presenting with polyuria and polydipsia and is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The clinical manifestations of this disorder vary greatly depending on different mutations. The present study reports the genetic, clinical and biochemical characteristics of patients with FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and four individual cases diagnosed with FNDI were included. Biochemical markers and magnetic resonance imaging (MRI) were evaluated and genomic DNA was sequenced. The results revealed that age at onset ranged from 1.0 to 11.0 years. Daily urine volumes ranged from 2.0 to 12.0 liters. One patient had mental retardation and three patients had puberty retardation; one patient had nausea, vomiting and mental retardation; and two patients had fever. Treatments, if given, included desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high-intensity signals were absent in two cases and present in four cases. Sequencing revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of the present study indicate that FNDI exhibits different clinical manifestations and a diverse age at onset. Posterior pituitary MRI does not provide a definite diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an enhanced understanding of FNDI pathogenesis may provide a basis for the development of presymptomatic FNDI diagnotic tools.

View Figures

View References

1	de Fost M, van Trotsenburg AS, van Santen HM, Endert E, van den Elzen C, Kamsteeg EJ, Swaab DF and Fliers E: Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene. Eur J Endocrinol. 165:161–165. 2011. View Article : Google Scholar : PubMed/NCBI
2	Kronenberg H and Williams RH: Williams textbook of endocrinology. Saunders/Elsevier; Philadelphia, PA: 2008
3	Wesche D, Deen PM and Knoers NV: Congenital nephrogenic diabetes insipidus: The current state of affairs. Pediatr Nephrol. 27:2183–2204. 2012. View Article : Google Scholar : PubMed/NCBI
4	Lee YW, Lee KW, Ryu JW, Mok JO, Ki CS, Park HK, Kim YJ, Kim SJ, Byun DW, Suh KI, et al: Mutation of Glu78 of the AVP-NPII gene impairs neurophysin as a carrier protein for arginine vasopressin in a family with neurohypophyseal diabetes insipidus. Ann Clin Lab Sci. 38:12–14. 2008.PubMed/NCBI
5	Ye D, Dong F, Lu W, Zhang Z, Lu X, Li C and Liu Y: A missense mutation in the arginine-vasopressin neurophysin-II gene causes autosomal dominant neurohypophyseal diabetes insipidus in a Chinese family. Clin Endocrinol (Oxf). 78:920–925. 2013. View Article : Google Scholar
6	Duzenli D, Saglar E, Deniz F, Azal O, Erdem B and Mergen H: Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus. Endocrine. 42:664–669. 2012. View Article : Google Scholar : PubMed/NCBI
7	Gu F, Jin Z and Zhang D: The etiology and clinical characteristics of central diabetes insipidus, a retrospective study of 408 cases. Zhonghua Yi Xue Za Zhi. 81:1166–1171. 2001.In Chinese.
8	Russell TA, Ito M, Ito M, Yu RN, Martinson FA, Weiss J and Jameson JL: A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons. J Clin Invest. 112:1697–1706. 2003. View Article : Google Scholar : PubMed/NCBI
9	Brachet C, Birk J, Christophe C, Tenoutasse S, Velkeniers B, Heinrichs C and Rutishauser J: Growth retardation in untreated autosomal dominant familial neurohypophyseal diabetes insipidus caused by one recurring and two novel mutations in the vasopressin-neurophysin II gene. Eur J Endocrinol. 164:179–187. 2011. View Article : Google Scholar
10	Fujisawa I: Magnetic resonance imaging of the hypothalamic-neurohypophyseal system. J Neuroendocrinol. 16:297–302. 2004. View Article : Google Scholar : PubMed/NCBI
11	Babey M, Kopp P and Robertson GL: Familial forms of diabetes insipidus: Clinical and molecular characteristics. Nat Rev Endocrinol. 7:701–714. 2011. View Article : Google Scholar : PubMed/NCBI
12	Ito M, Mori Y, Oiso Y and Saito H: A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus. J Clin Invest. 87:725–728. 1991. View Article : Google Scholar : PubMed/NCBI
13	Luo Y, Wang B, Qiu Y, Zhang C, Jin C, Zhao Y, Zhu Q and Ma X: Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin-neurophysin II gene. Endocrine. 42:208–213. 2012. View Article : Google Scholar : PubMed/NCBI
14	Christensen JH and Rittig S: Familial neurohypophyseal diabetes insipidus - an update. Semin Nephrol. 26:209–223. 2006. View Article : Google Scholar : PubMed/NCBI
15	Abu Libdeh A, Levy-Khademi F, Abdulhadi-Atwan M, Bosin E, Korner M, White PC and Zangen DH: Autosomal recessive familial neurohypophyseal diabetes insipidus: Onset in early infancy. Eur J Endocrinol. 162:221–226. 2010. View Article : Google Scholar
16	Rutishauser J, Böni-Schnetzler M, Böni J, Wichmann W, Huisman T, Vallotton MB and Froesch ER: A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: Cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab. 81:192–198. 1996.PubMed/NCBI
17	Beuret N, Rutishauser J, Bider MD and Spiess M: Mechanism of endoplasmic reticulum retention of mutant vasopressin precursor caused by a signal peptide truncation associated with diabetes insipidus. J Biol Chem. 274:18965–18972. 1999. View Article : Google Scholar : PubMed/NCBI
18	de Bree FM and Burbach JP: Structure-function relationships of the vasopressin prohormone domains. Cell Mol Neurobiol. 18:173–191. 1998. View Article : Google Scholar : PubMed/NCBI
19	Siggaard C, Rittig S, Corydon TJ, Andreasen PH, Jensen TG, Andresen BS, Robertson GL, Gregersen N, Bolund L and Pedersen EB: Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation. J Clin Endocrinol Metab. 84:2933–2941. 1999.PubMed/NCBI
20	Si-Hoe SL, De Bree FM, Nijenhuis M, Davies JE, Howell LM, Tinley H, Waller SJ, Zeng Q, Zalm R, Sonnemans M, et al: Endoplasmic reticulum derangement in hypothalamic neurons of rats expressing a familial neurohypophyseal diabetes insipidus mutant vasopressin transgene. FASEB J. 14:1680–1684. 2000.PubMed/NCBI
21	Arima H and Oiso Y: Mechanisms underlying progressive polyuria in familial neurohypophysial diabetes insipidus. J Neuroendocrinol. 22:754–757. 2010.PubMed/NCBI