Primary polydipsia in a family with a known mutation in the AVP gene

2014 ◽  
Author(s):  
Ruth Casey ◽  
Anne Marie Hannon ◽  
Caroline Joyce ◽  
Susan O'Connell ◽  
Domhnall O'Halloran
Keyword(s):  
Primary Polydipsia ◽  
Avp Gene

scholarly journals Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel missense mutation in AVP gene in a large Italian kindred

Endocrine ◽  
2021 ◽  
Author(s):  
Carlotta Marzocchi ◽  
Silvia Cantara ◽  
Alfonso Sagnella ◽  
Maria Grazia Castagna ◽  
Marco Capezzone
Keyword(s):  
Diabetes Insipidus ◽  
Missense Mutation ◽  
Autosomal Dominant ◽  
Three Dimensional ◽  
Rare Condition ◽  
Central Diabetes Insipidus ◽  
Disulfide Bridges ◽  
Italian Family ◽  
Avp Gene

Abstract Purpose Familial neurohypophysial diabetes insipidus (FNDI), commonly caused by autosomal dominant arginine vasopressin (AVP) mutations, is a rare condition in which vasopressin fails in regulating body’s level of water with final polyuria and polydipsia. Genetic testing in familial cases of FNDI should be carry out to ensure adequate treatments and avoid disease manifestations especially in infants. Methods In this study, we investigated three-generations of a large Italian family with clinical diagnosis of familial central diabetes insipidus for the presence of potential pathogenic mutations in the AVP gene. Results We identified a heterozygous missense mutation (c.154 T > A; p.C52S) in AVP gene in all affected members studied of a large Italian family. In silico tools were used to investigate the pathogenic role of the mutation and three-dimensional protein structure predicted that the p.C52S impairs disulfide bridges formation resulting in misfolding of the protein. Conclusions This is the first study that identified a novel missense p.C52S mutation as causative of central diabetes insipidus in a large Italian pedigree.

Impairment of osmotically stimulated AVP release in patients with primary polydipsia

1993 ◽  
Vol 265 (6) ◽  
pp. R1247-R1252 ◽  
Author(s):  
A. M. Moses ◽  
B. Clayton
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Plasma Osmolality ◽  
Normal Subjects ◽  
Urine Concentration ◽  
Published Data ◽  
Posterior Pituitary ◽  
Primary Polydipsia ◽  
Number Of Factors

The secretion of arginine vasopressin (AVP) from the posterior pituitary is primarily and finely regulated by the osmolality of plasma. Even though a number of factors alter osmolality-induced release of AVP, there are no published data in humans that have addressed the role of chronic overhydration on this phenomenon. To address this problem we have identified eight patients with primary polydipsia using criteria not involving measurement of AVP, and have subjected them to standardized infusions of hypertonic saline. These patients had less AVP in both plasma and urine in relation to plasma osmolality than was found in normal subjects. In addition, their rate of rise of plasma and urine AVP was less than in normal subjects. Their osmotic threshold for AVP release may have been higher than normal. These data demonstrate that chronic overhydration in humans downregulates the release of AVP in response to hypertonicity. This phenomenon may explain the impairment of urine concentration in patients with primary polydipsia and emphasizes the basis of the difficulty that may occur clinically in differentiating between patients with primary polydipsia and partial central diabetes insipidus.

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.

Effects of acute salt loading on vasopressin mRNA level in the rat brain

1994 ◽  
Vol 266 (5) ◽  
pp. R1591-R1595 ◽  
Author(s):  
M. Shoji ◽  
T. Kimura ◽  
Y. Kawarabayasi ◽  
K. Ota ◽  
M. Inoue ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Mrna Level ◽  
Mutual Relationship ◽  
Salt Loading ◽  
Complementary Dna ◽  
Osmotic Stimulation ◽  
Osmotic Challenge ◽  
Size Heterogeneity ◽  
The Brain ◽  
Avp Gene

To assess the mutual relationship between acute osmotic stimulation and arginine vasopressin (AVP) gene expression, 2 ml/100 g body weight of 0.9 M NaCl was intraperitoneally administered into conscious rats. They were decapitated to collect blood and brain samples before and 15 min and 1, 3, 6, and 9 h after the injection. The total RNA from the hypothalamus or whole brain tissue was used to determine AVP mRNA by Northern blot analyses with a complementary DNA probe. Plasma AVP and osmolality increased rapidly and transiently 15 min and 1 and 3 h after the injection. AVP mRNA was detected in the hypothalamus but not in the brain tissue without hypothalamus under basal and stimulated conditions. Brain AVP mRNA increased 2.2-fold at 3 h and 1.7-fold at 6 h (P < 0.05-0.01). These increases appeared to be due to the appearance of AVP mRNA with the shorter migration in the gel. These results suggest that an acute osmotic challenge increases AVP mRNA with size heterogeneity within the hypothalamo-hypophyseal tract.

A Novel Synonymous Variant in the AVP Gene Associated with Autosomal Dominant Familial Neurohypophyseal Diabetes Insipidus Causes Partial RNA Missplicing

2018 ◽  
Vol 107 (2) ◽  
pp. 167-180
Author(s):  
Helene Kvistgaard ◽  
Jane H. Christensen ◽  
Jan-Ove Johansson ◽  
Niels Gregersen ◽  
Charlotte Siggaard Rittig ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Laser Scanning ◽  
Dna Analysis ◽  
Autosomal Dominant ◽  
Challenge Test ◽  
Family Members ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Synonymous Variant ◽  
Avp Gene

Objective: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is characterized by severe polyuria and polydipsia and is caused by variations in the gene encoding the AVP prohormone. This study aimed to ascertain a correct diagnosis, to identify the underlying genetic cause of adFNDI in a Swedish family, and to test the hypothesis that the identified synonymous exonic variant in the AVP gene (c.324G>A) causes missplicing and endoplasmic reticulum (ER) retention of the prohormone. Design/Patients: Three affected family members were admitted for fluid deprivation test and dDAVP (1-deamino-8-d-arginine-vasopressin) challenge test. Direct sequencing of the AVP gene was performed in the affected subjects, and genotyping of the identified variant was performed in family members. The variant was examined by expression of AVP minigenes containing the entire coding regions as well as intron 2 of AVP. Methods/Results: Clinical tests revealed significant phenotypical variation with both complete and partial adFNDI phenotype. DNA analysis revealed a synonymous c.324G>A substitution in one allele of the AVP gene in affected family members only. Cellular studies revealed both normally spliced and misspliced pre-mRNA in cells transfected with the AVP c.324G>A minigene. Confocal laser scanning microscopy showed collective localization of the variant prohormone to ER and vesicular structures at the tip of cellular processes. Conclusion: We identified a synonymous variant affecting the second nucleotide of exon 3 in the AVP gene (c.324G>A) in a family in which adFNDI segregates. Notably, we showed that this variant causes partial missplicing of pre-mRNA, resulting in accumulation of the variant prohormone in ER. Our study suggests that even a small amount of aberrant mRNA might be sufficient to disturb cellular function, resulting in adFNDI.

scholarly journals A 27-Month-Old Boy with Polyuria and Polydipsia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Yvonne Lee ◽  
Erica Winnicki ◽  
Lavjay Butani ◽  
Stephanie Nguyen
Keyword(s):  
Child Development ◽  
Anxiety Disorders ◽  
Psychiatric Disorder ◽  
Water Deprivation ◽  
Fluid Intake ◽  
Laboratory Studies ◽  
Psychogenic Polydipsia ◽  
Water Drinking ◽  
Primary Polydipsia ◽  
Psychiatric Disturbances

Psychogenic polydipsia is a well-described phenomenon in those with a diagnosed psychiatric disorder such as schizophrenia and anxiety disorders. Primary polydipsia is differentiated from psychogenic polydipsia by the lack of a clear psychotic disturbance. We present a case of a 27-month-old boy who presented with polyuria and polydipsia. Laboratory studies, imaging, and an observed water deprivation test were consistent with primary polydipsia. Polydipsia resolved after family limited his fluid intake and began replacing water drinking with other transition objects and behaviors for self-soothing. This case highlights the importance of water deprivation testing to differentiate between causes of polyuria, thereby avoiding misdiagnosis and iatrogenic hyponatremia. Secondly, primary polydipsia can result during the normal stages of child development without overt psychiatric disturbances.

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