Glu-47, which forms a salt bridge between neurophysin-II and arginine vasopressin, is deleted in patients with familial central diabetes insipidus

1993 ◽  
Vol 77 (3) ◽  
pp. 600-604 ◽  
Author(s):  
H. Yuasa
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Salt Bridge ◽  
Central Diabetes Insipidus ◽  
Neurophysin Ii

scholarly journals Early-onset central diabetes insipidus is associated with de novo arginine vasopressin–neurophysin II or Wolfram syndrome 1 gene mutations

2015 ◽  
Vol 172 (4) ◽  
pp. 461-472 ◽  
Author(s):  
Silverio Perrotta ◽  
Natascia Di Iorgi ◽  
Fulvio Della Ragione ◽  
Saverio Scianguetta ◽  
Adriana Borriello ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Early Onset ◽  
De Novo ◽  
Novel Mutation ◽  
Wolfram Syndrome ◽  
Central Diabetes Insipidus ◽  
Nucleotide Position ◽  
Exon 2 ◽  
Neurophysin Ii

ObjectiveIdiopathic early-onset central diabetes insipidus (CDI) might be due to mutations of arginine vasopressin–neurophysin II (AVP–NPII (AVP)) or wolframin (WFS1) genes.Design and methodsSequencing of AVP and WFS1 genes was performed in nine children with CDI, aged between 9 and 68 months, and negative family history for polyuria and polydipsia.ResultsTwo patients carried a mutation in the AVP gene: a heterozygous G-to-T transition at nucleotide position 322 of exon 2 (c.322G>T) resulting in a stop codon at position 108 (p.Glu108X), and a novel deletion from nucleotide 52 to 54 (c.52_54delTCC) producing a deletion of a serine at position 18 (p.Ser18del) of the AVP pre-prohormone signal peptide. A third patient carried two heterozygous mutations in the WFS1 gene localized on different alleles. The first change was A-to-G transition at nucleotide 997 in exon 8 (c.997A>G), resulting in a valine residue at position 333 in place of isoleucine (p.Ile333Val). The second novel mutation was a 3 bp insertion in exon 8, c.2392_2393insACG causing the addition of an aspartate residue at position 797 and the maintenance of the correct open reading frame (p. Asp797_Val798insAsp). While similar WFS1 protein levels were detected in fibroblasts from healthy subjects and from the patient and his parents, a major sensitivity to staurosporine-induced apoptosis was observed in the patient fibroblasts as well as in patients with Wolfram syndrome.ConclusionsEarly-onset CDI is associated with de novo mutations of the AVP gene and with hereditary WFS1 gene changes. These findings have valuable implications for management and genetic counseling.

scholarly journals Identification of Mutations of the Arginine Vasopressin-Neurophysin II Gene in Two Kindreds with Familial Central Diabetes Insipidus

1998 ◽  
Vol 83 (2) ◽  
pp. 693-696 ◽  
Author(s):  
Christina Heppner ◽  
Jörg Kotzka ◽  
Catharina Bullmann ◽  
Wilhelm Krone ◽  
Dirk Müller-Wieland
Keyword(s):  
Diabetes Insipidus ◽  
Missense Mutation ◽  
Signal Peptide ◽  
Arginine Vasopressin ◽  
Family Members ◽  
Central Diabetes Insipidus ◽  
Nucleotide Position ◽  
Coding Region ◽  
Control Subjects ◽  
Neurophysin Ii

Familial central diabetes insipidus is transmitted as an autosomal dominant trait with almost complete penetrance. Twenty-three different mutations of the arginine vasopressin-neurophysin II gene have been reported to date, located within the signal peptide-, the arginine vasopressin-, or the neurophysin II-coding region. In the present study two kindreds with familial central diabetes insipidus were examined. The entire coding region of the arginine vasopressin-neurophysin II gene of one affected subject of each family was amplified by PCR and subcloned into a pUC 18 plasmid, and six positive clones were sequenced. After identification of the mutation, direct sequencing was performed on the respective sequence of family members and 28 healthy control subjects. In family A, a missense mutation (C→T) at nucleotide position 280 was detected, predicting the substitution of alanine by valine at position −1 of the signal peptide. All affected subjects were heterozygote for the mutation, whereas none of the unaffected family members or control subjects displayed the mutant sequence. In family B, a missense mutation within the neurophysin II-coding sequence was identified (nucleotide 1757, G→C), predicting the substitution of glycine by arginine at position 23. Again, affected family members were found to be heterozygote for the mutation, which was not observed in unaffected family members or in control subjects. Although the mutation of family A was recently described in 3 other kindreds as well, the mutation within the neurophysin II-coding region represents a novel mutation of the AVP-NP II gene.

scholarly journals MON-078 WFS1 Related Disorder in A 4-Month Old Girl

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Kleanthis Kleanthous ◽  
Emmanouil Manolakos ◽  
Eleni Dermitzaki ◽  
Andreas Fretzayas ◽  
Fumihiko Urano ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Early Onset ◽  
De Novo ◽  
Central Diabetes Insipidus ◽  
Hormone Deficiency ◽  
Bright Spot ◽  
Pediatric Endocrinology ◽  
Related Disorder ◽  
Neurophysin Ii

Abstract Background: Idiopathic early-onset central diabetes insipidus (CDI) may be due to mutations of arginine vasopressin-neurophysin II (AVP-NPII (AVP)) or wolframin (WFS1/2) genes (1). Clinical Case: A 4-month old girl presented to our pediatric endocrinology clinic due to severe polydipsia-polyphagia and polyuria. Plasma and urine glucose and HbA1c were normal and 24h monitoring of urinary output was elevated (4.2ml/kg/h). We proceeded to a modified 5-h water deprivation test followed by 0.1 mcg DDAVP IM. Results were compatible with partial central DI: at 5-hrs weight loss 5%, urine osmolality 155 from 111 at 0΄and 355 mOsm/kg 2hrs after DDAVP administration. Pituitary MRI was normal with presence of posterior pituitary bright spot and normal pituitary stalk. We initiated therapy with oral desmopressin acetate titrated at the dose of 70mcg x 3/day under close clinical and biochemical surveillance. Hyponatremia, with high natriuresis >100 mmol/L and elevated BNP occurred the 3rd day. Fludrocortisone 100 mcg x 2/day controlled natriuresis and supplemental oral NaCl 15% 15ml/day was needed to restore normal electrolytes (2). Marked catch-up growth was observed already at 1 month for height, weight and head circumference. Methods: Whole exome sequencing was performed targeted to a gene panel related to DI, containing AVP gene, WFS1/2 genes and AVPR2/AQP2 genes. Result: Two heterozygous variants were revealed: WFS1:NM_001145853:exon8:c. G997A:p.V333I,WFS1:NM_006005:exon8:c.G997A:p.V333I and WFS1:NM_00114585 3:exon8:c.G1832A:p.R611H,WFS1:NM_006005:exon8:c.G1832A:p.R611H reported as possibly damaging in 1/6 and 4/6 prediction programs respectively. These variants will be checked in both parents to confirm the presumed compound heterozygosity pattern in the child. Conclusion: We present a 4-month old girl with two heterozygous variants of WFS1 gene which may cause early-onset central diabetes insipidus and possibly a WFS1 related disorder (1). Reference: (1) Perrotta S 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 Apr;172(4):461-72 (2) Papadimitriou DT, Spiteri A, Attilakos A, Papadimitriou A. Cerebral Salt Wasting Complicated by Central Diabetes Insipidus and Growth Hormone Deficiency. Indian J Pediatr. 2018 Jul;85(7):580-581

Low arginine vasopressin levels in patients with central diabetes insipidus is not associated with anaemia

2019 ◽  
Author(s):  
Benedict Morin ◽  
Bettina Winzeler ◽  
Julie Refardt ◽  
Cornelia Imber ◽  
Wiebke Fenske ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Central Diabetes Insipidus

scholarly journals Transcriptomic Analysis Reveals that Atf3/c-Jun/Lgals3 axis is associated with Central Diabetes Insipidus after Hypothalamic Injury

2021 ◽  
Author(s):  
Mingfeng Zhou ◽  
Yichao Ou ◽  
Guangsen Wu ◽  
Kai Li ◽  
Junjie Peng ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Body Fluid ◽  
Microglial Activation ◽  
The Body ◽  
Transcriptomic Analysis ◽  
Central Diabetes Insipidus ◽  
Electrolyte Imbalance ◽  
Hypothalamic Injury ◽  
Vasopressin Neurons

Background: Hypothalamic injury causes several complicated neuroendocrine-associated disorders, such as water-electrolyte imbalance, obesity, and hypopituitarism. Among these, central diabetes insipidus (CDI), characterized by polyuria, polydipsia, low urine specific gravity, and deficiency of arginine vasopressin contents, is a typical complication after hypothalamic injury. Methods: CDI was induced by hypothalamic pituitary stalk injury in male animals. Behavioral parameters and blood sample were collected to evaluate the characteristics of body fluid metabolism imbalance. The brains were harvested for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in corresponding hypothalamic nuclei. Results: Based on transcriptomic analysis, we demonstrated the upregulation of the Atf3/c-Jun axis and identified Lgals3, a microglial activation related gene, as the most significant target gene in response to the body fluid imbalance in CDI. Furthermore, we found that the microglia possessed elevated phagocytic ability, which could promote the elimination of arginine vasopressin neurons after hypothalamic injury. Conclusion: Our findings suggested that the Atf3/c-Jun/Lgals3 axis was associated with the microglial activation, and might participate in the loss of functional arginine vasopressin neurons in CDI after hypothalamic injury.

scholarly journals Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases

2015 ◽  
Vol 172 (3) ◽  
pp. K11-K17 ◽  
Author(s):  
Giuseppe Bellastella ◽  
Antonio Bizzarro ◽  
Ernesto Aitella ◽  
Mariluce Barrasso ◽  
Domenico Cozzolino ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Post Partum ◽  
Central Diabetes Insipidus ◽  
Pituitary Function ◽  
Unsuccessful Attempt ◽  
Function Recovery ◽  
History Of ◽  
In Pregnancy

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in thepost partumperiod, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine–vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month ofpost partumperiod respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational orpost partumautoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

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