AVP-NPII gene mutations and clinical characteristics of the patients with autosomal dominant familial central diabetes insipidus

Abstract

Familial central DI is a progressive disease, and age of onset of symptoms can differ depending on the mutation. Bright spot on pituitary MRI might be present at onset, but become invisible over time. Genetic testing and appropriate counseling should be given in familial cases of central DI to ensure adequate treatment, and to avoid chronic water deprivation that might result in growth retardation in childhood.

Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel nonsense mutation in AVP‑NPII gene

“…As a result, the prohormone is likely retained within the endoplasmic reticulum and exceeds its capacity to Previous studies have described the MRI presentation of subjects with FNDI. In one study, the presence of a bright spot in the posterior lobe appeared to vary between members of the same family (5). In another case series, such a spot was entirely absent from all 13 patients (24).…”

“…Three-dimensional structural models of the predicted wild-type and mutant proteins were generated and comparisons between the proteins were performed using the PHYRE2 Protein Fold Recognition Server database (http://wwwsbg.bio. ic.ac.uk/phyre2) and the SWISS-MODEL protein structure homology-modelling server (http://swissmodel.expasy.org) as reported previously (5).…”

“…Familial neurohypophyseal diabetes insipidus (FNDI) is a rare inherited disease that accounts for only 1% of central diabetes insipidus cases (2). The disorder usually presents in early childhood with polyuria and polydipsia, and follow-up evaluation frequently reveals loss of the posterior pituitary bright spot on T1-weighted magnetic resonance imaging (MRI) (3)(4)(5). FNDI is caused by mutations of the arginine vasopressin-neurophysin II (AVP-NPII) gene (GenBank ID, NM_000490.4), which is located on chromosome 20 and encodes a preproprotein that is proteolytically processed to generate multiple products, including AVP, neurophysin II and copeptin (6).…”

Diagnosis and Treatment of Hypopituitarism

“…In these patients, there is a loss of GnRH neurons in the hypothalamus which leads to GnRH deficiencies and hypogonadotropic hypogonadism (the lack of secondary sex characteristics) in conjunction with olfactory loss (anosmia or hyposmia) that is due to olfactory bulb loss or hypoplasia [ 10 ]. There is also a condition known as neurohypophyseal (familial) diabetes insipidus that is triggered by mutations of the neurophysin II part of the vasopressin-neurophysin precursor genes [ 11 ]. Due to these mutations, the precursor genes do not divide into vasopressin and neurophysin II which, in turn, causes an excessive accumulation of the precursor substance within the cells that leads to the eventual death of the hypothalamic neurons (apoptosis) in which these genes are expressed.…”

“…Due to these mutations, the precursor genes do not divide into vasopressin and neurophysin II which, in turn, causes an excessive accumulation of the precursor substance within the cells that leads to the eventual death of the hypothalamic neurons (apoptosis) in which these genes are expressed. Depending on the genetic disorders or degree of the mutation, the symptoms manifest immediately after the birth or during childhood [ 11 ].…”