Central Diabetes Insipidus Caused by Arginine Vasopressin Gene Mutation: Report of a Novel Mutation and Review of Literature

Abstract

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant hereditary disorder characterized by severe polydipsia and polyuria that usually presents in early childhood. In this study, we describe a new arginine vasopressin (AVP) gene mutation in an ethnic German family with FNDI and provide an overview of disease-associated AVP-gene mutations that are already described in literature. Three members of a German family with neurohypophyseal diabetes insipidus were studied. Isolated DNA from peripheral blood samples was used for mutation analysis by sequencing the whole coding region of AVP-NPII gene. Furthermore, we searched the electronic databases MEDLINE (Pubmed) as well as HGMD, LOVD-ClinVar, db-SNP and genomAD in order to compare our cases to that of other patients with FNDI. Genetic analysis of the patients revealed a novel heterozygote missense mutation in exon 2 of the AVP gene (c.274T>G), which has not yet been described in literature. We identified reports of more than 90 disease-associated mutations in the AVP gene in literature. The novel mutation of the AVP gene seems to cause FNDI in the presented German family. Similar to our newly detected mutation, most mutations causing FNDI are found in exon 2 of the AVP gene coding for neurophysin II. Clinically, it is important to think of FNDI in young children presenting with polydipsia and polyuria.

Key words

desmopressin - AVP-NPII gene - neurohypophyseal diabetes insipidus - AVP

Publication History

Received: 01 March 2020

Accepted after revision: 06 May 2020

Article published online:
06 July 2020

• References

• 1 DeGroot LJ, Jameson JL. Endocrinology. 5th ed. USA: Elsevier Saunders; 2006: 544-549
• 2 Luo Y, Wang B, Qiu Y. et al. 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 2012; 42: 208-213
• 3 Land H, Schutz G, Schmale H. et al. Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor. Nature 1982; 295: 299-303
• 4 Christensen JH, Siggaard C, Corydon TJ. et al. Six novel mutations in the arginine vasopressin gene in 15 kindreds with autosomal dominant familial neurohypophyseal diabetes insipidus give further insight into the pathogenesis. Eur J Hum Genet 2004; 12: 44-51
• 5 Arima H, Azuma Y, Morishita Y. et al. Central diabetes insipidus. Nagoya J Med Sci 2016; 78: 349-358
• 6 Rittig S, Siggaard C, Ozata M. et al. Autosomal dominant neurohypophyseal diabetes insipidus due to substitution of histidine for tyrosine (2) in the vasopressin moiety of the hormone precursor. J Clin Endocrinol Metab 2002; 87: 3351-3355
• 7 Willcutts MD, Felner E, White PC. Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin. Hum Mol Genet 1999; 8: 1303-1307
• 8 Brachet C, Birk J, Christophe C. et al. 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 2011; 164: 179-187
• 9 Bahnsen U, Oosting P, Swaab DF. et al. A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus. EMBO J 1992; 11: 19-23
• 10 Calvo B, Bilbao JR, Rodriguez A. et al. Molecular analysis in familial neurohypophyseal diabetes insipidus: early diagnosis of an asymptomatic carrier. J Clin Endocrinol Metab 1999; 84: 3351-3354
• 11 Heppner C, Kotzka J, Bullmann C. et al. Identification of mutations of the arginine vasopressin-neurophysin II gene in two kindreds with familial central diabetes insipidus. J Clin Endocrinol Metab 1998; 83: 693-696
• 12 Stephen MD, Fenwick RG, Brosnan PG. Polyuria and polydipsia in a young child: diagnostic considerations and identification of novel mutation causing familial neurohypophyseal diabetes insipidus. Pituitary 2012; 15 (Suppl 1) S1-S5
• 13 Gagliardi PC, Bernasconi S, Repaske DR. Autosomal dominant neurohypophyseal diabetes insipidus associated with a missense mutation encoding Gly23-->Val in neurophysin II. J Clin Endocrinol Metab 1997; 82: 3643-3646
• 14 Repaske DR, Browning JE. A de novo mutation in the coding sequence for neurophysin-II [Pro24-->Leu] is associated with onset and transmission of autosomal dominant neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab 1994; 79: 421-427
• 15 Wolf MT, Dotsch J, Metzler M. et al. A new missense mutation of the vasopressin-neurophysin II gene in a family with neurohypophyseal diabetes insipidus. Horm Res 2003; 60: 143-147
• 16 Skordis N, Patsalis PC, Hettinger JA. et al. A novel arginine vasopressin-neurophysin II mutation causes autosomal dominant neurohypophyseal diabetes insipidus and morphologic pituitary changes. Horm Res 2000; 53: 239-245
• 17 Santiprabhob J, Browning J, Repaske D. A missense mutation encoding Cys73Phe in neurophysin II is associated with autosomal dominant neurohypophyseal diabetes insipidus. Mol Genet Metab 2002; 77: 112-118
• 18 Miyakoshi M, Kamoi K, Murase T. et al. Novel mutant vasopressin-neurophysin II gene associated with familial neurohypophyseal diabetes insipidus. Endocr J 2004; 51: 551-556
• 19 Jendle J, Christensen JH, Kvistgaard H. et al. Late-onset familial neurohypophyseal diabetes insipidus due to a novel mutation in the AVP gene. Clin Endocrinol (Oxf) 2012; 77: 586-592
• 20 Grant FD, Ahmadi A, Hosley CM. et al. Two novel mutations of the vasopressin gene associated with familial diabetes insipidus and identification of an asymptomatic carrier infant. J Clin Endocrinol Metab 1998; 83: 3958-3964
• 21 Ito M, Mori Y, Oiso Y. et al. A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus. J Clin Invest 1991; 87: 725-758
• 22 Melo ME, Marui S, Brito VN. et al. Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel mutation in arginine-vasopressin gene in a Brazilian family. Arq Bras Endocrinol Metabol 2008; 52: 1272-1276
• 23 Nagasaki H, Ito M, Yuasa H. et al. Two novel mutations in the coding region for neurophysin-II associated with familial central diabetes insipidus. J Clin Endocrinol Metab 1995; 80: 1352-1356
• 24 Ueta Y, Taniguchi S, Yoshida A. et al. A new type of familial central diabetes insipidus caused by a single base substitution in the neurophysin II coding region of the vasopressin gene. J Clin Endocrinol Metab 1996; 81: 1787-1790
• 25 Rutishauser J, Kopp P, Gaskill MB. et al. A novel mutation [R97C] in the neurophysin moiety of prepro-vasopressin-neurophysin II associated with autosomal-dominant neurohypophyseal diabetes insipidus. Mol Genet Metab 1999; 67: 89-92
• 26 Baglioni S, Corona G, Maggi M. et al. Identification of a novel mutation in the arginine vasopressin-neurophysin II gene affecting the sixth intrachain disulfide bridge of the neurophysin II moiety. Eur J Endocrinol 2004; 151: 605-611
• 27 DiMeglio LA, Gagliardi PC, Browning JE. et al. A missense mutation encoding cys (67) --> gly in neurophysin ii is associated with early onset autosomal dominant neurohypophyseal diabetes insipidus. Mol Genet Metab 2001; 72: 39-44
• 28 Elias PC, Elias LL, Torres N. et al. Progressive decline of vasopressin secretion in familial autosomal dominant neurohypophyseal diabetes insipidus presenting a novel mutation in the vasopressin-neurophysin II gene. Clin Endocrinol (Oxf) 2003; 59: 511-518
• 29 Rutishauser J, Kopp P, Gaskill MB. et al. Clinical and molecular analysis of three families with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel and recurrent mutations in the vasopressin-neurophysin II gene. Eur J Endocrinol 2002; 146: 649-656
• 30 Fujii H, Iida S, Moriwaki K. Familial neurohypophyseal diabetes insipidus associated with a novel mutation in the vasopressin-neurophysin II gene. Int J Mol Med 2000; 5: 229-234
• 31 Calvo B, Bilbao JR, Urrutia I. et al. Identification of a novel nonsense mutation and a missense substitution in the vasopressin-neurophysin II gene in two Spanish kindreds with familial neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab 1998; 83: 995-997
• 32 Bullmann C, Kotzka J, Grimm T. et al. Identification of a novel mutation in the arginine vasopressin-neurophysin II gene in familial central diabetes insipidus. Exp Clin Endocrinol Diabetes 2002; 110: 134-137
• 33 de Fost M, van Trotsenburg AS, van Santen HM. et al. Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene. Eur J Endocrinol 2011; 165: 161-165
• 34 Wahlstrom JT, Fowler MJ, Nicholson WE. et al. A novel mutation in the preprovasopressin gene identified in a kindred with autosomal dominant neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab 2004; 89: 1963-1968
• 35 Fluck CE, Deladoey J, Nayak S. et al. Autosomal dominant neurohypophyseal diabetes insipidus in a Swiss family, caused by a novel mutation (C59Delta/A60W) in the neurophysin moiety of prepro-vasopressin-neurophysin II (AVP-NP II). Eur J Endocrinol 2001; 145: 439-444
• 36 Yuasa H, Ito M, Nagasaki H. et al. Glu-47, which forms a salt bridge between neurophysin-II and arginine vasopressin, is deleted in patients with familial central diabetes insipidus. J Clin Endocrinol Metab 1993; 77: 600-604
• 37 Tae HJ, Baek KH, Shim SM. et al. A novel splice site mutation of the arginine vasopressin-neurophysin II gene identified in a kindred with autosomal dominant familial neurohypophyseal diabetes insipidus. Mol Genet Metab 2005; 86: 307-313
• 38 Christensen JH, Kvistgaard H, Knudsen J. et al. A novel deletion partly removing the AVP gene causes autosomal recessive inheritance of early-onset neurohypophyseal diabetes insipidus. Clin Genet 2013; 83: 44-52
• 39 Lindenthal V, Mainberger A, Morris-Rosendahl DJ. et al. Dilatative uropathy as a manifestation of neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin-II gene. Klin Padiatr 2013; 225: 407-412
• 40 Patti G, Scianguetta S, Roberti D. et al. Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene. Eur J Endocrinol 2019; 181: 233-244
• 41 Ilhan M, Tiryakioglu NO, Karaman O. et al. A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes insipidus. J Endocrinol Invest 2016; 39: 285-290
• 42 Birkegaard C, Christensen JH, Falorni A. et al. A novel variation in the AVP gene resulting in familial neurohypophyseal diabetes insipidus in a large Italian kindred. Pituitary 2013; 16: 152-157
• 43 Tian D, Cen J, Nie M. et al. Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus. Int J Mol Med 2016; 38: 1243-1249
• 44 Kobayashi H, Fujisawa I, Ikeda K. et al. A novel heterozygous missense mutation in the vasopressin moiety is identified in a Japanese person with neurohypophyseal diabetes insipidus. J Endocrinol Invest 2006; 29: 252-256
• 45 Chitturi S, Harris M, Thomsett MJ. et al. Utility of AVP gene testing in familial neurohypophyseal diabetes insipidus. Clin Endocrinol (Oxf) 2008; 69: 926-930
• 46 Hrckova G, Janko V, Kytnarova J. et al. Two novel mutations in seven Czech and Slovak kindreds with familial neurohypophyseal diabetes insipidus-benefit of genetic testing. Eur J Pediatr 2016; 175: 1199-1207
• 47 Lee YW, Lee KW, Ryu JW. 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 2008; 38: 12-14
• 48 Garcia-Castano A, Madariaga L, Perez de Nanclares G. et al. Forty-one individuals with mutations in the AVP-NPII gene associated with familial neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab 2020; 105
• 49 Rittig S, Robertson GL, Siggaard C. et al. Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus. Am J Hum Genet 1996; 58: 107-117
• 50 Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol 2005; 16: 2836-2846
• 51 Toustrup LB, Kvistgaard H, Palmfeldt J. et al. The novel Ser18del AVP variant causes inherited neurohypophyseal diabetes insipidus by mechanisms shared with other signal peptide variants. Neuroendocrinology 2018; 106: 167-186
• 52 Qureshi S, Galiveeti S, Bichet DG. et al. Diabetes insipidus: celebrating a century of vasopressin therapy. Endocrinology 2014; 155: 4605-4621
• 53 Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 1975; 94: 441-448
• 54 Perrotta S, Di Iorgi N, Ragione FD. et al. Early-onset central diabetes insipidus is associated with de novo arginine vasopressin-neurophysin II or Wolfram syndrome 1 gene mutations. Eur J Endocrinol 2015; 172: 461-472
• 55 Abbes AP, Engel H, Klomp C, Bruggeman EJ. Gene symbol: AVP. Disease: Diabetes insipidus, neurohypophyseal. Accession #Hm0561. Hum Genet 2006; Feb 118(6): 784
• 56 Rutishauser J, Spiess M, Kopp P. Genetic forms of neurohypophyseal diabetes insipidus. Best Pract Res Clin Endocrinol Metab 2016; 30: 249-262
• 57 Birk J, Friberg MA, Prescianotto-Baschong C. et al. Dominant pro-vasopressin mutants that cause diabetes insipidus form disulfide-linked fibrillar aggregates in the endoplasmic reticulum. J Cell Sci 2009; 122 (Pt 21): 3994-4002
• 58 Christensen JH, Rittig S. Familial neurohypophyseal diabetes insipidus–an update. Semin Nephrol 2006; 26: 209-223
• 59 Spiess M, Friberg M, Beuret N. et al. Role of protein aggregation and degradation in autosomal dominant neurohypophyseal diabetes insipidus. Mol Cell Endocrinol 2019; 501: 110653
• 60 Hagiwara D, Grinevich V, Arima H. A novel mechanism of autophagy-associated cell death of vasopressin neurons in familial neurohypophysial diabetes insipidus. Cell Tissue Res 2019; 375: 259-266
• 61 Tamma G, Goswami N, Reichmuth J. et al. Aquaporins, vasopressin, and aging: current perspectives. Endocrinology 2015; 156: 777-788
• 62 Repaske DR, Medlej R, Gultekin EK. et al. Heterogeneity in clinical manifestation of autosomal dominant neurohypophyseal diabetes insipidus caused by a mutation encoding Ala-1-->Val in the signal peptide of the arginine vasopressin/neurophysin II/copeptin precursor. J Clin Endocrinol Metab 1997; 82: 51-56
• 63 Siggaard C, Christensen JH, Corydon TJ. et al. Expression of three different mutations in the arginine vasopressin gene suggests genotype-phenotype correlation in familial neurohypophyseal diabetes insipidus kindreds. Clin Endocrinol (Oxf) 2005; 63: 207-216
• 64 De Goeij DC, Binnekade R, Tilders FJ. Chronic stress enhances vasopressin but not corticotropin-releasing factor secretion during hypoglycemia. Am J Physiol 1992; 263 (2 Pt 1) E394-E399
• 65 Caraty A, Grino M, Locatelli A. et al. Insulin-induced hypoglycemia stimulates corticotropin-releasing factor and arginine vasopressin secretion into hypophysial portal blood of conscious, unrestrained rams. J Clin Invest 1990; 85: 1716-1721
• 66 Chiodera P, Volpi R, Capretti L. et al. Hypoglycemia-induced arginine vasopressin and oxytocin release is mediated by glucoreceptors located inside the blood-brain barrier. Neuroendocrinology 1992; 55: 655-659
• 67 Alexander SL, Roud HK, Irvine CHG. Effect of insulin-induced hypoglycaemia on secretion patterns and rates of corticotrophin-releasing hormone, arginine vasopressin and adrenocorticotrophin in horses. J Endocrinol 1997; 153: 401-409
• 68 Kacheva S, Kolk K, Morgenthaler NG. et al. Gender-specific co-activation of arginine vasopressin and the hypothalamic-pituitary-adrenal axis during stress. Clin Endocrinol (Oxf) 2015; 82: 570-576