Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032617 (polyuria)
 3,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Autosomal dominant neurohypophyseal diabetes insipidus is a rare form of central diabetes insipidus that is caused by mutations in the vasopressin-neurophysin II (AVP-NPII) gene. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP). Here we report a case of familial neurohypophyseal diabetes insipidus in four generations of a Korean family, caused by heterozygous missense mutation in exon 2 of the AVP-NPII gene (c.286G>T). This is the first report of such a case in Korea.
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PMID:Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a mutation in the arginine-vasopressin II gene in four generations of a Korean family. 2565 69

Familial neurohypophyseal diabetes insipidus (FNDI) is a disorder characterized by excess excretion of diluted urine (polyuria) and increased uptake of fluids (polydipsia). The disorder is caused by mutations affecting the AVP-NPII gene, resulting in absent or deficient secretion of the antidiuretic hormone arginine vasopressin (AVP) by the neurohypophysis. In this study we examined a three-generation Cypriot kindred suspected to have FNDI. Direct sequencing analysis of AVP-NPII identified a missense mutation (NM_000490.4:c.61T>C; p.Tyr21His; rs121964893) within the AVP moiety on exon 1 of the gene in all affected family members. So far, only three studies have reported mutations within the AVP moiety of AVP-NPIIas being associated with FNDI, with the vast majority of identified FNDI mutations being located within the signalling peptide or the neurophysis II (NPII) moiety of the gene. The mutation within the AVP moiety identified here had been reported previously in a Turkish kindred with FNDI. Consequently, the findings of this study confirm the causal role of mutations within the AVP moiety in FNDI. Herein we review reported mutations within the AVP moiety of AVP-NPII and their contribution to FNDI.
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PMID:Identification of an AVP-NPII mutation within the AVP moiety in a family with neurohypophyseal diabetes insipidus: review of the literature. 2623 32

Familial 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.
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PMID:Central Diabetes Insipidus Caused by Arginine Vasopressin Gene Mutation: Report of a Novel Mutation and Review of Literature. 3262 14