Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structural genes for human prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NPII; ARVP) locus and prepro-oxytocin-neurophysin-I (prepro-OT-NPI; OT) locus are closely linked separated by only 12 kilobasepairs of DNA. These two loci have been assigned to chromosome 20 by previous studies of somatic cell hybrids. We used Southern blots to analyze a restriction fragment length polymorphism detected by a probe for prepro-OT-NPI to determine the linkage relationships for the ARVP/OT loci using samples from the Centre d'Etude du Polymorphisme Humain (Paris, France) collection of families. The ARVP/OT loci demonstrated extremely close linkage with the prodynorphin (PDYN) locus, with no recombinants (theta of 0) and a log10 odds score of 5.2. Previous observations have shown the ARVP and PDYN peptides to be coexcreted in the same neurosecretory granules of some pituitary axons and that increased transcription of both genes occurs with osmotic stimulation. The combined ARVP/PT/PDYN group was also found to demonstrate linkage with other anonymous DNA segments on chromosome 20, including D20S4, D20S5, and D20S6. Using multilocus linkage analysis, the ARVP/OT loci map to the distal short arm of chromosome 20 about 15 centimorgans toward the telomere from the D20S5 locus, which is located near the middle of the short arm at 20p 12.21. These linkage relationships establish that the secretory and transcriptional associations of ARVP and PDYN extend to a close physical relationship in the human genome. Furthermore, the restriction fragment length polymorphism detected by these loci can serve as accurate markers in segregation studies of putative defects involving the OT, ARVP, or PDYN loci as well as provide a tool for studying the location of other genes, such as GH-releasing hormone.
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PMID:Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin-neurophysin-I to prodynorphin and other loci on chromosome 20. 197 46

The human genes for prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NPII) and prepro-oxytocin-neurophysin I (prepro-OT-NPI) were cloned from a human genomic library and the nucleotide sequence of both genes was determined. The two genes are similar in their intron-exon structure, linked together with 12 kilobases intervening, and transcribed from opposite DNA strands. A human small cell lung cancer cell line, H378, produces significant quantities of pre-pro-AVP-NPII mRNA using a transcription unit predicted from the genomic DNA sequence. Despite the proximity of the actively transcribed prepro-AVP-NPII gene, transcription of prepro-OT-NPI is not detected in this cell line.
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PMID:The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line. 299 Dec 79

The advances in our understanding of the pathophysiology of defects in the antidiuretic hormone, the V2 receptor and the water channel, owing to mutations in the prepro-AVP-NPII, AVPR2 and AQP2 genes respectively, is providing insight into inherited diabetes insipidus as well as the more numerous sporadic cases. Further structure-function analyses of these mutated genes will increase our understanding of normal vasopressin-regulated water transport across the kidney epithelium at the molecular level.
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PMID:Diabetes insipidus. 757 30

Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is an inherited disease caused by progressive degeneration of the magnocellular neurons of the hypothalamus leading to decreased ability to produce the hormone arginine vasopressin (AVP). Affected individuals are not symptomatic at birth, but usually develop diabetes insipidus at 1-6 yr of age. The genetic locus of the disease is the AVP-neurophysin II (NPII) gene, and mutations that cause ADNDI have been found in both the signal peptide of the prepro-AVP-NPII precursor and within NPII itself. An affected girl who presented at 9 months of age and her similarly affected younger brother and father were all found to have a novel missense mutation (G1758-->T) encoding the amino acid substitution Gly23-->Val within NPII. The mutation was confirmed by restriction endonuclease analysis. A T1-weighted magnetic resonance imaging of the father's pituitary gland demonstrates an attenuated posterior pituitary bright spot. This mutation may be valuable for developing models of dominantly inherited neurodegeneration, as the early age of onset of symptoms suggests that this mutation may be particularly deleterious to the magnocellular neuron.
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PMID:Autosomal dominant neurohypophyseal diabetes insipidus associated with a missense mutation encoding Gly23-->Val in neurophysin II. 936 May 20

Autosomal-dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by heterozygous mutations in the gene encoding vasopressin-neurophysin II (AVP-NPII) on chromosome 20p13. We analyzed the AVP-NP II gene in a family with adFNDI by direct sequencing. A novel C to T transition (289C-->T in the cDNA, resulting in the substitution of Arg 97 by Cys (R97C) in the prepro-AVP-NPII precursor molecule) was identified in the gene region encoding neurophysin II in the index patient. This amino acid change is thought to result in the formation of an incorrectly folded hormone precursor, which may lead to chronic neurotoxicity and explain the dominant inheritance of the disease.
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PMID:A novel mutation (R97C) in the neurophysin moiety of prepro-vasopressin-neurophysin II associated with autosomal-dominant neurohypophyseal diabetes insipidus. 1032 29

The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations of the gene that codes for the vasopressin-neurophysin II (AVP-NPII) precursor. The aims of the present study were to relate the clinical phenotype to the specific genotype and to the molecular genetic effects of the most frequently reported adFNDI mutation located at the cleavage site of the signal peptide of AVP-NPII [Ala(-1)Thr]. Genetic analysis and clinical studies of AVP secretion, urinary AVP, and urine output were performed in 16 affected and 16 unaffected family members and 11 spouses of a Danish adFNDI kindred carrying the Ala(-1)Thr mutation. Mutant complementary DNA carrying the same mutation was expressed in a neurogenic cell line (Neuro2A), and the cellular effects were studied by Western blotting, immunocytochemistry, and AVP measurements. The clinical studies showed a severe progressive deficiency of plasma and urinary AVP that manifested during childhood. The expression studies demonstrated that the Ala(- 1)Thr mutant cells produced 8-fold less AVP than wild-type cells and accumulated excessive amounts of 23-kDa NPII protein corresponding to uncleaved prepro-AVP-NPII. Furthermore, a substantial portion of the intracellular AVP-NPII precursor appeared to be colocalized with an endoplasmic reticulum antigen (Grp78). These results provide independent confirmation that this Ala(-1)Thr mutation produces adFNDI by directing the production of a mutant preprohormone that accumulates in the endoplasmic reticulum, because it cannot be cleaved from the signal peptide and transported to neurosecretory vesicles for further processing and secretion.
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PMID:Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation. 1044 1

To determine the genetic basis of autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) in a Cypriot family, we ascertained and studied a large, four-generation kindred in which all participating family members had arginine vasopressin-neurophysin II (AVP-NP-II) gene analyses done. A G to A transition was found by DNA sequence analysis at position 1773 (G1773A) of the AVP-NPII gene which is predicted to encode a substitution of tyrosine for cysteine in codon 59 (CYS59TYR). The mutation was confirmed by restriction endonuclease analysis of PCR amplification products that contain the corresponding segment of the AVP-NPII gene. To clarify the morphologic status of the pituitaries of family members, 12 affected and 3 nonaffected members had magnetic resonance imaging (MRI) studies. The bright spot of the posterior pituitary lobe was completely absent in 75% and faintly identified in 25% of the affected members who were examined with MRI. We conclude that (1) a novel G1773A transition in exon 2 of the AVP-NPII gene causes ADNDI in the large Cypriot kindred studied, (2) this mutation is predicted to encode a CYS59TYR substitution in NPII, and (3) MRI studies of the posterior pituitary lobes of affected family members show either a decreased intensity or a complete absence of the bright spot in all cases studied.
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PMID:A novel arginine vasopressin-neurophysin II mutation causes autosomal dominant neurohypophyseal diabetes insipidus and morphologic pituitary changes. 1115 Aug 85

The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) has been linked to 40 different mutations of the gene encoding the vasopressin-neurophysin II (AVP-NPII) precursor. All of these mutations have been located in either the signal peptide or neurophysin II moiety. We now report a three-generation Turkish kindred in which severe adFNDI cosegregates with a novel missense mutation in the part of the AVP-NPII gene encoding the AVP moiety. This mutation (T-->C at position 285 in the genomic sequence) was found in only one allele and predicts a substitution of histidine for tyrosine at position 2 in AVP. Like other adFNDI mutations, this substitution is expected to impair folding and processing of the precursor, in this case by interfering with normal binding of the AVP and NPII moieties. It is associated clinically with inability to concentrate urine during fluid deprivation, a greater than 80% deficiency of AVP secretion, and absence of the posterior pituitary bright spot on magnetic resonance imaging. These findings are consistent with the hypothesis that mutations in the AVP-NPII gene cause adFNDI by directing the production of a folding incompetent precursor that prevents the expression of the normal allele via a cytotoxic effect on the magnocellular neurons.
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PMID:Autosomal dominant neurohypophyseal diabetes insipidus due to substitution of histidine for tyrosine(2) in the vasopressin moiety of the hormone precursor. 1210 48

Familial neurohypophyseal diabetes insipidus (FNDI; OMIM 192340) is a rare inherited disorder with an autosomal dominant inheritance pattern. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP). We report a Korean kindred in whom FNDI is associated with a novel deletion mutation in exon 2 of the AVP-NPII gene encoding the neurophysin II moiety. An 18-yr-old man with polyuria and polydipsia was shown to have central diabetes insipidus by using the water deprivation test. Four family members were suspected to have symptomatic vasopressin-deficient diabetes insipidus. Direct sequencing of the AVP-NPII gene showed a heterozygous GAG deletion mutation in exon 2, which results in in-frame deletion of glutamic acid (c.232_234delGAG; p.Glu78del). The mutation was predicted to yield an abnormal AVP precursor lacking Glu78 (E78) in its neurophysin II moiety. Because Glu78 is essential for neurophysin II molecules to form a salt bridge with AVP, the function of neurophysin as a carrier protein for AVP would be impaired. The proband's mother and sister have the same mutation. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the appropriate expression of vasopressin.
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PMID:Mutation of Glu78 of the AVP-NPII gene impairs neurophysin as a carrier protein for arginine vasopressin in a family with neurohypophyseal diabetes insipidus. 1831 76

We report the case of an infant boy with polyuria and a familial history of central diabetes insipidus. Laboratory blood tests disclosed hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Plasma magnesium concentration was slightly low. Urine analysis showed hypercalciuria, hyposthenuria, and high excretion of potassium. Such findings oriented toward type III Bartter syndrome (BSIII). Direct sequencing of the CLCNKB gene revealed no disease-causing mutations. The water deprivation test was positive. Magnetic resonance imaging showed a lack of posterior pituitary hyperintensity. Finally, direct sequencing of the AVP-NPII gene showed a point mutation (c.1884G>A) in a heterozygous state, confirming an autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). This condition did not explain the patient's phenotype; thus, we investigated for Gitelman syndrome (GS). A direct sequencing of the SLC12A3 gene showed c.269A>C and c.1205C>A new mutations. In conclusion, the patient had a genetic combination of GS and adFNDI with a BSIII-like phenotype.
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PMID:Type III Bartter-like syndrome in an infant boy with Gitelman syndrome and autosomal dominant familial neurohypophyseal diabetes insipidus. 2482 90


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