scholarly journals Identification of a novel mutation in the arginine vasopressin-neurophysin II gene affecting the sixth intrachain disulfide bridge of the neurophysin II moiety

2004 ◽  
pp. 605-611 ◽  
Author(s):  
S Baglioni ◽  
G Corona ◽  
M Maggi ◽  
M Serio ◽  
A Peri
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Neuronal Degeneration ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Peripheral Blood Lymphocytes ◽  
Dimensional Structure ◽  
Coding Region ◽  
Exon 2 ◽  
Neurophysin Ii

OBJECTIVE: Most mutations of the arginine vasopressin-neurophysin II (AVP-NPII) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). Such mutations are predicted to alter the three-dimensional structure of the prohormone, which accumulates in the cell body, ultimately leading to neuronal degeneration and hormonal deficit. In this study we describe the case of a 26-year-old female reporting a long-lasting history of polyuria/polydipsia. The father of the patient was affected by diabetes insipidus and was under desmopressin treatment until the time of his death. Nevertheless, the patient had never been subjected to endocrine evaluation. DESIGN AND METHODS: Clinical and genetic studies were performed. An 8-h fluid deprivation test plus desmopressin challenge and a 5% saline solution test were performed, in order to confirm the diagnosis. DNA was extracted from peripheral blood lymphocytes and subjected to direct sequencing of the entire coding region of the AVP-NPII gene. RESULTS AND CONCLUSIONS: Clinical assessment of the patient confirmed the diagnosis of neurohypophyseal diabetes insipidus. Desmopressin treatment was started, which effectively reversed the polyuria/ polydipsia syndrome. Genetic analysis revealed a novel mutation (1665T>A) in exon 2 of the AVP-NPII gene, disrupting one of the disulfide bonds present in the NPII moiety which play a fundamental role in determining the proper folding of the molecule. In summary, in the present study we have described a novel mutation of the AVP-NPII gene, which is consistent with the malfolding/toxicity hypothesis underlying the pathogenesis of adFNDI.

Central Diabetes Insipidus Caused by Arginine Vasopressin Gene Mutation: Report of a Novel Mutation and Review of Literature

2020 ◽  
Vol 52 (11) ◽  
pp. 796-802
Author(s):  
Lara L.I. Feldkamp ◽  
Elke Kaminsky ◽  
Tina Kienitz ◽  
Marcus Quinkler
Keyword(s):  
Diabetes Insipidus ◽  
Gene Mutation ◽  
Arginine Vasopressin ◽  
Novel Mutation ◽  
Gene Mutations ◽  
Coding Region ◽  
Exon 2 ◽  
German Family ◽  
Gene Coding ◽  
Avp Gene

AbstractFamilial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant hereditary disorder characterized by severe polydipsia and polyuria that usually presents in early childhood. In this study, we describe a new arginine vasopressin (AVP) gene mutation in an ethnic German family with FNDI and provide an overview of disease-associated AVP-gene mutations that are already described in literature. Three members of a German family with neurohypophyseal diabetes insipidus were studied. Isolated DNA from peripheral blood samples was used for mutation analysis by sequencing the whole coding region of AVP-NPII gene. Furthermore, we searched the electronic databases MEDLINE (Pubmed) as well as HGMD, LOVD-ClinVar, db-SNP and genomAD in order to compare our cases to that of other patients with FNDI. Genetic analysis of the patients revealed a novel heterozygote missense mutation in exon 2 of the AVP gene (c.274T>G), which has not yet been described in literature. We identified reports of more than 90 disease-associated mutations in the AVP gene in literature. The novel mutation of the AVP gene seems to cause FNDI in the presented German family. Similar to our newly detected mutation, most mutations causing FNDI are found in exon 2 of the AVP gene coding for neurophysin II. Clinically, it is important to think of FNDI in young children presenting with polydipsia and polyuria.

scholarly journals Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin–neurophysin II gene

2011 ◽  
Vol 165 (1) ◽  
pp. 161-165 ◽  
Author(s):  
M de Fost ◽  
A S P van Trotsenburg ◽  
H M van Santen ◽  
E Endert ◽  
C van den Elzen ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Water Deprivation ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Resonance Imaging ◽  
Exon 2 ◽  
Hyperintense Signal ◽  
The Brain ◽  
Neurophysin Ii

BackgroundFamilial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin–neurophysin II (AVP–NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with autosomal dominant neurohypophyseal DI caused by a novel mutation.CaseA thirty-four-year-old woman and her three-year-old son were evaluated because of polyuria and polydipsia since the age of 1.5 years onwards. Both patients were subjected to a water deprivation test confirming the diagnosis of central DI. Magnetic resonance imaging of the brain of the mother showed a hypothalamus without apparent abnormalities and a relatively small neurohypophysis without a hyperintense signal. Mutation analysis showed a c.322G>T (p.?/p.Glu108X) in Exon 2 of the AVP–NPII gene in both mother and son.DiscussionThis study reports neurohypophyseal DI in a mother and her son due to a novel mutation in Exon 2 of the AVP–NPII gene. Clinical and pathophysiological aspects of this disease are shortly reviewed and discussed.

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 Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel mutation in arginine-vasopressin gene in a Brazilian family

2008 ◽  
Vol 52 (8) ◽  
pp. 1272-1276 ◽  
Author(s):  
Maria Edna de Melo ◽  
Suemi Marui ◽  
Vinícius Nahime de Brito ◽  
Marcio Corrêa Mancini ◽  
Berenice B. Mendonca ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Sequencing Analysis ◽  
The Novel ◽  
Autosomal Dominant Disorder ◽  
Vasopressin Gene ◽  
Avp Gene

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare autosomal dominant disorder characterized by polyuria and polydipsia due to deficiency of arginine vasopressin (AVP). More than 50 mutations causing adFNDI have been already reported in the AVP gene. The aim of the present study is to analyze the AVP gene in four generations of one Brazilian kindred with adFNDI. The proband was a 31-year old female with huge hypotonic polyuria (10 L/day) dated from childhood. Molecular analysis included amplification of all exons and exon-intron regions of the AVP gene by PCR and direct sequencing. Sequencing analysis showed a novel point mutation in heterozygous: G88V (GGC>GTC). All affected patients presented the same mutation also in heterozygous, while it was absent in four normal members. We expand the repertoire of mutations in AVP describing the novel G88V mutation in one Brazilian kindred with adFNDI.

Dilatative Uropathy as a Manifestation of Neurohypophyseal Diabetes Insipidus due to a Novel Mutation in the Arginine Vasopressin-Neurophysin-II Gene

2013 ◽  
Vol 225 (07) ◽  
pp. 407-412 ◽  
Author(s):  
V. Lindenthal ◽  
A. Mainberger ◽  
D. Morris-Rosendahl ◽  
L. Löning ◽  
W. Mayer ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Novel Mutation ◽  
Neurophysin Ii

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.

A novel mutation in the coding region for neurophysin-II is associated with autosomal dominant neurohypophyseal diabetes insipidus

1996 ◽  
Vol 44 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Frank Rauch ◽  
Claudia Lenzner ◽  
Peter Nürnberg ◽  
Cornelius Frömmel ◽  
Ulrich Vetter
Keyword(s):  
Diabetes Insipidus ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Coding Region ◽  
Neurophysin Ii

A Novel Mutation of the Vasopressin-Neurophysin II Gene in a Familial Neurohypophyseal Diabetes Insipidus

2007 ◽  
Vol 22 (2) ◽  
pp. 118
Author(s):  
Mi Jung Kim ◽  
Byung Wan Lee ◽  
In Kyung Jeong ◽  
Jun Goo Kang ◽  
Seong Jin Lee ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Novel Mutation ◽  
Neurophysin Ii

scholarly journals Central Precocious Puberty in a Girl and Early Puberty in Her Brother Caused by a Novel Mutation in the MKRN3 Gene

2014 ◽  
Vol 99 (4) ◽  
pp. E647-E651 ◽  
Author(s):  
Nikolaos Settas ◽  
Catherine Dacou-Voutetakis ◽  
Maria Karantza ◽  
Christina Kanaka-Gantenbein ◽  
George P. Chrousos ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Novel Mutation ◽  
Structural Alignment ◽  
In Silico Analysis ◽  
Missense Variant ◽  
Central Precocious Puberty ◽  
Dimensional Structure ◽  
Sex Characteristics ◽  
Coding Region ◽  
Early Puberty

Context: Central precocious puberty (CPP), defined as the development of secondary sex characteristics prior to age 8 years in girls and 9 years in boys, results from the premature activation of the hypothalamic-pituitary-gonadal axis. Mutations in the imprinted gene MKRN3 have been recently implicated in familial cases of CPP. Objective: The objective of the study was to uncover the genetic cause of CPP in a family with two affected siblings. Design and participants: The entire coding region of the paternally expressed MKRN3 gene was sequenced in two siblings, a girl with CPP and her brother with early puberty, their parents, and their grandparents. Results: A novel heterozygous missense variant in the MKRN3 gene (p.C340G) was detected in the two affected siblings, their unaffected father, and the paternal grandmother. As expected, the mutated allele followed an imprinted mode of inheritance within the affected family. In silico analysis predicts the mutation as possibly damaging in all five software packages used. Furthermore, structural alignment of the ab initio native and mutant MKRN3 models predicts that the p.C340G mutation leads to significant structural perturbations in the 3-dimensional structure of the C3HC4 really interesting new gene motif of the protein, further emphasizing the functional implications of the novel MKRN3 alteration. Conclusions: We report a novel MKRN3 mutation (p.C340G) in a girl with CPP and her brother with early puberty. MKRN3 alterations should be suspected in all cases with familial CPP or early puberty, especially if male patients are also involved or the precocious puberty trend does not follow the usually observed mother-to-daughter inheritance.

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