A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes insipidus

İlhan, Muzaffer; Tiryakioglu, Necip Ozan; Karaman, Ozcan; Çoşkunpınar, Ender; Yildiz, Rabia Sevda; Turgut, Seda; Tiryakioglu, Duygu; Toprak, Hüseyin; Taşan, Ertuğrul

doi:10.1007/s40618-015-0357-9

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…The present study defines clinical and molecular characteristics of 22 affected patients with familial central DI from 13 different Italian families. Eight of the identified mutations were known to be associated with adNDI of the AVP-NPII gene and have previously been reported by others (8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,34,35,36,37,38,39), while two novel mutations are here described for the first time. Genetic analyses revealed that all affected members were heterozygous for the mutations as expected from autosomal dominant mode of inheritance.…”

Section: Discussionmentioning

confidence: 54%

“…More than 70 disease-causing mutations resulting in a defective pro-hormone and a deficiency of AVP have been described in adNDI (8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30). The AVP-NPII gene consists of three exons where exon 1 encodes the signal peptide, the AVP peptide and the first nine amino acids of NPII; exon 2 encodes the majority of NPII and exon 3 encodes the carboxyl-terminal 17 amino acids of NPII and copeptin.…”

Section: Introductionmentioning

confidence: 99%

“…The wide variability in the age of onset and the severity of the AVP deficiency among patients with the same mutation may be ascribed to individual differences among such patients, like the rate of production of the mutant precursor, the intensity of neurohypophyseal stimulation, individual susceptibility to the toxic effect of the mutant precursor, the ability to degrade mutant precursors and variations in secretory reserve capacity or in the development of the gland itself (8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30). Recent data demonstrated that although autophagy should primarily be a protective mechanism, continuous autophagy leads to gradual loss of organelles including endoplasmic reticulum (ER), resulting in autophagyassociated cell death of AVP neurons in mice with familial NDI (33).…”

Section: Introductionmentioning

confidence: 99%

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Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene

Patti

Scianguetta

Roberti

et al. 2019

European Journal of Endocrinology

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Background Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone. Aim To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus. Patients and methods We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating. Results Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype–phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed the absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case. Conclusion adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene

Patti

Scianguetta

Roberti

et al. 2019

European Journal of Endocrinology

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“…Among the more than 70 different adFNDI-causing variants identified in the AVP gene, 8 affect the region encoding the signal peptide (SP) of the AVP preprohormone [3,19,20], and 1 is located immediately upstream in the 5′ UTR [21]. Only 2 of these variants have previously been studied in cell lines (Ala19Thr and g.227delG) [5,8,[22][23][24], and 1 of these (Ala19Thr) has additionally been introduced into the mouse genome [12].…”

Section: Introductionmentioning

confidence: 99%

The Novel Ser18del AVP Variant Causes Inherited Neurohypophyseal Diabetes Insipidus by Mechanisms Shared with Other Signal Peptide Variants

Toustrup¹,

Kvistgaard²,

Palmfeldt

et al. 2017

Neuroendocrinology

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Background/Aim: Variability in the severity and age at onset of autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) may be associated with certain types of variants in the arginine vasopressin (AVP) gene. In this study, we aimed to describe a large family with an apparent predominant female occurrence of polyuria and polydipsia and to determine the underlying cause. Methods: The family members reported their family demography and symptoms. Two subjects were diagnosed by fluid deprivation and dDAVP challenge tests. Eight subjects were tested genetically. The identified variant along with 3 previously identified variants in the AVP gene were investigated by heterologous expression in a human neuronal cell line (SH-SY5Y). Results: Both subjects investigated clinically had a partial neurohypophyseal diabetes insipidus phenotype. A g.276_278delTCC variant in the AVP gene causing a Ser18del deletion in the signal peptide (SP) of the AVP preprohormone was perfectly co-segregating with the disease. When expressed in SH-SY5Y cells, the Ser18del variant along with 3 other SP variants (g.227G>A, Ser17Phe, and Ala19Thr) resulted in reduced AVP mRNA, impaired AVP secretion, and partial AVP prohormone degradation and retention in the endoplasmic reticulum. Impaired SP cleavage was demonstrated directly in cells expressing the Ser18del, g.227G>A, and Ala19Thr variants, using state-of-the-art mass spectrometry. Conclusion: Variants affecting the SP of the AVP preprohormone cause adFNDI with variable phenotypes by a mechanism that may involve impaired SP cleavage combined with effects at the mRNA, protein, and cellular level.

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“…Arginine vasopressin (AVP) is known to be involved in the water intake behaviors of animals [ 25 , 26 , 27 ]. AVP and aldosterone (ALD) are secreted by the neurohypophysis in response to increased angiotensin II (ANG II) levels [ 28 ] and blood osmolality [ 29 , 30 , 31 ].…”

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confidence: 99%

Brain Formaldehyde is Related to Water Intake behavior

Li¹,

Su²,

He³

et al. 2016

Aging and disease

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A promising strategy for the prevention of Alzheimer’s disease (AD) is the identification of age-related changes that place the brain at risk for the disease. Additionally, AD is associated with chronic dehydration, and one of the significant changes that are known to result in metabolic dysfunction is an increase in the endogenous formaldehyde (FA) level. Here, we demonstrate that the levels of uric formaldehyde in AD patients were markedly increased compared with normal controls. The brain formaldehyde levels of wild-type C57 BL/6 mice increased with age, and these increases were followed by decreases in their drinking frequency and water intake. The serum arginine vasopressin (AVP) concentrations were also maintained at a high level in the 10-month-old mice. An intravenous injection of AVP into the tail induced decreases in the drinking frequency and water intake in the mice, and these decreases were associated with increases in brain formaldehyde levels. An ELISA assay revealed that the AVP injection increased both the protein level and the enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO), which is an enzyme that produces formaldehyde. In contrast, the intraperitoneal injection of formaldehyde increased the serum AVP level by increasing the angiotensin II (ANG II) level, and this change was associated with a marked decrease in water intake behavior. These data suggest that the interaction between formaldehyde and AVP affects the water intake behaviors of mice. Furthermore, the highest concentration of formaldehyde in vivo was observed in the morning. Regular water intake is conducive to eliminating endogenous formaldehyde from the human body, particularly when water is consumed in the morning. Establishing good water intake habits not only effectively eliminates excess formaldehyde and other metabolic products but is also expected to yield valuable approaches to reducing the risk of AD prior to the onset of the disease.

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A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes insipidus

Cited by 9 publications

References 33 publications

Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene

Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene

The Novel Ser18del AVP Variant Causes Inherited Neurohypophyseal Diabetes Insipidus by Mechanisms Shared with Other Signal Peptide Variants

Brain Formaldehyde is Related to Water Intake behavior

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