Identification of an AVP-NPII mutation within the AVP moiety in a family with neurohypophyseal diabetes insipidus: review of the literature
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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.
Key wordsArginine vasopressin Autosomal dominant Founder mutation Mutation Neurohypophyseal diabetes insipidus Sanger sequencing
- 4.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.Google Scholar
- 16.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.Google Scholar
- 19.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.CrossRefGoogle Scholar
- 21.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.Google Scholar