Autosomal Dominant Neurohypophyseal Diabetes Insipidus in Two Families

Abstract

Background: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease with symptoms of polydipsia, polyuria and dehydration caused by arginine vasopressin deficiency. Disease onset is within infancy or adolescence. A variety of disease-causing mutations of the arginine vasopressin neurophysin II gene (AVP) on chromosome 20p13 have been described. Methods: Two Polish families with adFNDI were screened for mutations. Processing of wild-type (WT) and mutant AVP was monitored using immunocytochemical methods in stably transfected Neuro2A cells. AVP secretion into the cell culture supernatant was investigated with an enzyme immunoassay. Results: In the first family a heterozygous p.G96D mutation was identified. Some patients additionally carried a novel heterozygous mutation p.A159T. The second family presented with a heterozygous mutation p.C98G. Confocal laser microscopy unveiled accumulation of p.G96D and p.C98G prohormones in the cellular bodies, whereas WT and p.A159T prohormones and/or processed products were located in the tips of cellular processes. Reduced levels of AVP in supernatant culture medium of p.G96D and p.C98G transfected cells in comparison to p.A159T and WT cells were found. Conclusions: We conclude that the p.G96D and p.C98G mutations cause adFNDI in the two reported families. The sequence variant p.A159T does not seem to have disease-causing effects.

Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a mutation in the arginine-vasopressin II gene in four generations of a Korean family

“…Neurohypophyseal DI is a rare disorder of water conservation resulting from a deficiency of AVP. Under normal circumstances, the precursor hormone prepro-AVP is produced by neurosecretory cells in the supraoptic and paraventricular nuclei of the human hypothalamus 8) . During axonal transport to the pituitary gland, prepro-AVP is cleaved to become AVP, and it is finally stored in the posterior pituitary gland (neurohypophysis).…”

“…The AVP-NPII gene is located on chromosome 20p13 and has three exons, with an open reading frame of 492 bp. Exon 1 encodes a signal peptide, AVP, and the N-terminal portion of NP II; exon 2 encodes the central region of NP II; and exon 3 encodes the C-terminal part of NP II and copeptin, a glycoprotein with an unknown function 8 , 13) . The mutations involved in familial neurophyphyseal DI include small deletions, as well as missense and nonsense mutations that affect the signal peptide, the AVP moiety, or the AVP carrier protein, NPII.…”