Abstract
Familial neurohypophyseal diabetes insipidus (FNDI) is a disorder characterized by excess excretion of diluted urine (polyuria) and increased uptake of fluids (polydipsia). The disorder is caused by mutations affecting the AVP-NPII gene, resulting in absent or deficient secretion of the antidiuretic hormone arginine vasopressin (AVP) by the neurohypophysis. In this study we examined a three-generation Cypriot kindred suspected to have FNDI. Direct sequencing analysis of AVP-NPII identified a missense mutation (NM_000490.4:c.61T>C; p.Tyr21His; rs121964893) within the AVP moiety on exon 1 of the gene in all affected family members. So far, only three studies have reported mutations within the AVP moiety of AVP-NPII as being associated with FNDI, with the vast majority of identified FNDI mutations being located within the signalling peptide or the neurophysis II (NPII) moiety of the gene. The mutation within the AVP moiety identified here had been reported previously in a Turkish kindred with FNDI. Consequently, the findings of this study confirm the causal role of mutations within the AVP moiety in FNDI. Herein we review reported mutations within the AVP moiety of AVP-NPII and their contribution to FNDI.
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Di Iorgi N, Napoli F, Allegri AE, et al, 2012 Diabetes insipidus—diagnosis and management. Horm Res Paediatr 77: 69–84.
Makaryus AN, McFarlane SI, 2006 Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med 73: 65–71.
Christensen JH, Rittig S, 2006 Familial neurohypophyseal diabetes insipidus—an update. Semin Nephrol 26: 209–223.
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 16: 152–157.
Rittig S, Robertson GL, Siggaard C, et al, 1996 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 58: 107–117.
Skordis N, Patsalis PC, Hettinger JA, et al, 2000 A novel arginine vasopressin-neurophysin II mutation causes autosomal dominant neurohypophyseal diabetes insipidus and morphologic pituitary changes. Horm Res 53: 239–245.
Christensen JH, Siggaard C, Corydon TJ, et al, 2004 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 12: 44–51.
Rittig S, Siggaard C, Ozata M, et al, 2002 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 87: 3351–3355.
Wahlstrom JT, Fowler MJ, Nicholson WE, Kovacs WJ, 2004 A novel mutation in the preprovasopressin gene identified in a kindred with autosomal dominant neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab 89: 1963–1968.
Kobayashi H, Fujisawa I, Ikeda K, et al, 2006 A novel heterozygous missense mutation in the vasopressin moiety is identified in a Japanese person with neurohypophyseal diabetes insipidus. J Endocrinol Invest 29: 252–256.
Untergasser A, Cutcutache I, Koressaar T, et al, 2012 Primer3—new capabilities and interfaces. Nucleic Acids Res 40: e115.
Kent WJ, 2002 BLAT—the BLAST-like alignment tool. Genome Res 12: 656–664.
Braverman LE, Mancini JP, McGoldrick DM, 1965 Hereditary idiopathic diabetes insipidus. A case report with autopsy findings. Ann Intern Med 63: 503–508.
Bergeron C, Kovacs K, Ezrin C, Mizzen C, 1991 Hereditary diabetes insipidus: an immunohistochemical study of the hypothalamus and pituitary gland. Acta Neuropathol 81: 345–348.
Russell TA, Ito M, Ito M, et al, 2003 A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons. J Clin Invest 112: 1697–1706.
Hagiwara D, Arima H, Morishita Y, et al, 2014 Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus. Cell Death Dis 27: e1148.
Ito M, Yu RN, Jameson JL, 1999 Mutant vasopressin precursors that cause autosomal dominant neurohypophyseal diabetes insipidus retain dimerization and impair the secretion of wild-type proteins. J Biol Chem 274: 9029–9037.
Hayashi M, Arima H, Ozaki N, et al, 2009 Progressive polyuria without vasopressin neuron loss in a mouse model for familial neurohypophysial diabetes insipidus. Am J Physiol Regul Integr Comp Physiol 296: R1641–1649.
Christensen JH, Siggaard C, Corydon TJ, et al, 2004 Differential cellular handling of defective arginine vasopressin (AVP) prohormones in cells expressing mutations of the AVP gene associated with autosomal dominant and recessive familial neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab 89: 4521–4531.
Moeller HB, Rittig S, Fenton RA, 2013 Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr Rev 34: 278–301.
Breslow E 1993 The conformation and functional domains of neurophysins. In: Gross P, Richter D, Robertson GL, (eds) Vasopressin. Paris: John Libbey Eurotext 143–157.
Willcutts MD, Feiner E, White PC, 1999 Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin. Hum Mol Genet 8: 1303–1307.
Shammas C, Neocleous V, Toumba M, et al, 2012 Overview of genetic defects in endocrinopathies in the island of Cyprus; evidence of a founder effect. Genet Test Mol Biomarkers 16: 1073–1079.
Skordis N, Patsalis PC, Bacopoulou I, Sismani C, Sultan C, Lumbroso S, 2005 5alpha-reductase 2 gene mutations in three unrelated patients of Greek Cypriot origin: identification of an ancestral founder effect. J Pediatr Endocrinol Metab 18: 241–246.
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Koufaris, C., Alexandrou, A., Sismani, C. et al. Identification of an AVP-NPII mutation within the AVP moiety in a family with neurohypophyseal diabetes insipidus: review of the literature. Hormones 14, 442–446 (2015). https://doi.org/10.14310/horm.2002.1604
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DOI: https://doi.org/10.14310/horm.2002.1604