scholarly journals Novel Variant of AVPR2 Giving Rise to X-Linked Congenital Nephrogenic Diabetes Insipidus in a 7-Month-Old Danish Boy

2020 ◽  
Vol 10 (3) ◽  
pp. 124-129
Author(s):  
Johanne Emy Sollid ◽  
Shivani Joshi ◽  
Malgorzata  Pulczynska Wason ◽  
Søren Rittig ◽  
Jane Hvarregaard Christensen ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Gene Encoding ◽  
Exon 2 ◽  
Congenital Nephrogenic Diabetes Insipidus ◽  
Novel Variant ◽  
Precise Diagnosis ◽  
The One

Patients affected with congenital nephrogenic diabetes insipidus (CNDI) have reduced ability to concentrate urine. Early diagnosis of CNDI is important to avoid recurrent episodes of severe dehydration. We present a Danish male suffering from typical symptoms and diagnosed with CNDI at the age of 7 months. Gene sequencing of this proband and his mother revealed a novel variant in the gene encoding the antidiuretic hormone receptor (<i>AVPR2</i>). The variant is a deletion of nucleotide c.151 in exon 2 of <i>AVPR2</i> (GenBank NM_000054.4:c.151del). This 1bp deletion is predicted to cause a frameshift that results in tryptophan replacing valine at position 51 in <i>AVPR2</i> and a premature stop codon three codons downstream (p.Val51Trpfs*3) likely resulting in faulty expression of the receptor. Identification of disease-causing variants such as the one described here contributes to precise diagnosis, especially in carriers and newborns, thus preventing the long-term physical and intellectual disability observed in some CNDI-patients.

scholarly journals Novel de novo AVPR2 Variant in a Patient with Congenital Nephrogenic Diabetes Insipidus

2017 ◽  
Vol 7 (3) ◽  
pp. 130-137 ◽  
Author(s):  
Shivani Joshi ◽  
Per Brandstrom ◽  
Niels Gregersen ◽  
Søren Rittig ◽  
Jane Hvarregaard Christensen
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
De Novo ◽  
Stop Codon ◽  
Exon 2 ◽  
Nonsense Mediated Decay ◽  
Direct Dna Sequencing ◽  
Congenital Nephrogenic Diabetes Insipidus

Early diagnosis and treatment of congenital nephrogenic diabetes insipidus (CNDI) are essential due to the risk of intellectual disability caused by repeated episodes of dehydration and rapid rehydration. Timely genetic testing for disease-causing variants in the arginine vasopressin receptor 2 (AVPR2) gene is possible in at-risk newborns with a known family history of X-linked CNDI. In this study, a Swedish male with no family history was diagnosed with CNDI at 6 months of age during an episode of gastroenteritis. We analyzed the coding regions of AVPR2 by PCR and direct DNA sequencing and identified an 80-bp duplication in exon 2 (GenBank NM_000054.4; c.800_879dup) in the proband. This variant leads to a frameshift and introduces a stop codon four codons downstream (p.Ala294Profs*4). The variant gene product either succumbs to nonsense-mediated decay or is translated to a truncated nonfunctional vasopressin V2 receptor. This variant was absent in four unaffected family members, including his parents, as well as in 100 alleles from healthy controls, and is thus considered a novel de novo disease-causing variant. Identification of the disease-causing variant facilitated precise diagnosis of CNDI in the proband. Furthermore, it allows future genetic counseling in the family. This case study highlights the importance of genetic testing in sporadic infant cases with CNDI that can occur due to de novo variants in AVPR2 or several generations of female transmission of the disease-causing variant.

scholarly journals A Novel Mutation in the AVPR2 Gene in a Palestinian Family with Nephrogenic Diabetes Insipidus

2017 ◽  
Vol 07 (01) ◽  
pp. e1-e3
Author(s):  
Abdulsalam Abu-Libdeh ◽  
Isaiah Wexler ◽  
Imad Dweikat ◽  
David Zangen ◽  
Bassam Abu-Libdeh
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Novel Mutation ◽  
Collecting Duct ◽  
Failure To Thrive ◽  
Male Infant ◽  
Gene Encoding ◽  
Exon 2 ◽  
Recessive Form ◽  
V2 Vasopressin Receptor

AbstractNephrogenic diabetes insipidus (NDI) is a urinary concentrating defect resulting from resistance of the collecting duct to the antidiuretic action of vasopressin (AVP). The X-linked recessive form is the most frequent genetic cause of inherited NDI and can be caused by mutations in the gene encoding the V2 vasopressin receptor (AVPR2). A Palestinian male infant presented in the neonatal period with failure to thrive, vomiting, irritability, fever, and polyuria, and had biochemical findings consistent with NDI. The diagnosis of NDI was established based on the clinical picture, absent response to desmopressin, and a similarly affected elder brother. Sequencing of the AVPR2 gene for the patient and his affected brother revealed a novel missense mutation with replacement of G by A in codon 82 located in exon 2 (TGC → TAC), causing a cysteine to tyrosine substitution (C82Y). Testing of the mother showed that she was the carrier of that mutation. This is the identified AVPR2 mutation in a Palestinian family. Knowledge of these mutations will allow genetic counseling and early diagnosis of affected males.

scholarly journals Congenital nephrogenic diabetes insipidus accompanied with central nephrogenic diabetes secondary to pituitary surgery -a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Zhang ◽  
Yimin Shen ◽  
Yuezhong Ren ◽  
Yvbo Xin ◽  
Lijun Wang
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Direct Detection ◽  
Urine Volume ◽  
Pituitary Surgery ◽  
Accurate Method ◽  
Heterozygous Mutation ◽  
Case Presentation ◽  
Congenital Nephrogenic Diabetes Insipidus

Abstract Background Diabetes insipidus (DI) can be a common cause of polydipsia and polyuria. Here, we present a case of congenital nephrogenic diabetes insipidus (CNDI) accompanied with central diabetes insipidus (CDI) secondary to pituitary surgery. Case presentation A 24-year-old Chinese woman came to our hospital with the complaints of polydipsia and polyuria for 6 months. Six months ago, she was detected with pituitary apoplexy, and thereby getting pituitary surgery. However, the water deprivation test demonstrated no significant changes in urine volume and urine gravity in response to fluid depression or AVP administration. In addition, the genetic results confirmed a heterozygous mutation in arginine vasopressin receptor type 2 (AVPR2) genes. Conclusions She was considered with CNDI as well as acquired CDI secondary to pituitary surgery. She was given with hydrochlorothiazide (HCTZ) 25 mg twice a day as well as desmopressin (DDAVP, Minirin) 0.1 mg three times a day. There is no recurrence of polyuria or polydipsia observed for more than 6 months. It can be hard to consider AVPR2 mutation in female carriers, especially in those with subtle clinical presentation. Hence, direct detection of DNA sequencing with AVPR2 is a convenient and accurate method in CNDI diagnosis.

scholarly journals Functional characterization of a loss-of-function mutant I324M of arginine vasopressin receptor 2 in X-linked nephrogenic diabetes insipidus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lixia Wang ◽  
Weihong Guo ◽  
Chunyun Fang ◽  
Wenli Feng ◽  
Yumeng Huang ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Nephrogenic Diabetes Insipidus ◽  
Functional Characterization ◽  
Gene Mutations ◽  
Biochemical Properties ◽  
Vasopressin Receptor ◽  
Inherited Disease ◽  
Loss Of Function ◽  
Gene Encoding

AbstractX-linked nephrogenic diabetes insipidus (X-linked NDI) is a rare inherited disease mainly caused by lost-of-function mutations in human AVPR2 gene encoding arginine vasopressin receptor 2 (V2R). Our focus of the current study is on exploration of the functional and biochemical properties of Ile324Met (I324M) mutation identified in a pedigree showing as typical recessive X-linked NDI. We demonstrated that I324M mutation interfered with the conformation of complex glycosylation of V2R. Moreover, almost all of the I324M-V2R failed to express on the cell surface due to being captured by the endoplasmic reticulum control system. We further examined the signaling activity of DDAVP-medicated cAMP and ERK1/2 pathways and the results revealed that the mutant receptor lost the ability in response to DDAVP stimulation contributed to the failure of accumulation of cAMP and phosphorylated ERK1/2. Based on the characteristics of molecular defects of I324M mutant, we selected two reagents (SR49059 and alvespimycin) to determine whether the functions of I324M-V2R can be restored and we found that both compounds can significantly “rescue” I324M mutation. Our findings may provide further insights for understanding the pathogenic mechanism of AVPR2 gene mutations and may offer some implications on development of promising treatments for patients with X-linked NDI.

scholarly journals Two Novel Mutations in the Aquaporin 2 Gene in a Girl with Congenital Nephrogenic Diabetes Insipidus

2005 ◽  
Vol 20 (6) ◽  
pp. 1076 ◽  
Author(s):  
Hae Il Cheong ◽  
Su Jin Cho ◽  
Shou Huan Zheng ◽  
Hee Yeon Cho ◽  
Il Soo Ha ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Novel Mutations ◽  
Aquaporin 2 ◽  
Congenital Nephrogenic Diabetes Insipidus

scholarly journals Integrating population variation and protein structural analysis to improve the clinical genetic diagnosis and treatment in children with congenital nephrogenic diabetes insipidus

2020 ◽  
Author(s):  
Panli LIAO ◽  
Tianchao XIANG ◽  
Hongxia LI ◽  
Ye FANG ◽  
Xiaoyan FANG ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Isotonic Saline ◽  
Population Variation ◽  
Pathogenic Mutations ◽  
Protein Structural Analysis ◽  
Congenital Nephrogenic Diabetes Insipidus

Abstract Background and Objectives: Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. Establishing the genetic diagnosis appears particularly important to NDI for early detection and differential diagnosis.Method: We utilized a Chinese multicenter registry to investigate genotype and phenotype in children with NDI from 2014 to 2019. The structural locations of the pathogenic mutations from this study and the literature, as well as population variants retried from gnomAD were analyzed. Results: A total of 10 boys from 9 families carried mutations in AVPR2 (8/10) or AQP2 (2/10). Another 7 relatives of the families were diagnosed by sequencing for partial or subclinical NDI. Patients presented with dehydration, polyuria-polydipsia, and severe hypernatremia with a median age at diagnosis of 1.0 month (IQR 0.16, 18). Protein structural analysis revealed a notable clustering of diagnostic mutations in the transmembrane regions of AVPR2, and enrichment of diagnostic mutations by autosomal dominant inheritance (AD) in the C terminal region of AQP2. The pathogenic mutations are significantly more likely to be buried inside the domain comparing the population variants. Through structural analysis and in silico prediction, the eight mutations identified in this study were considered as presumably disease causative. The most common treatments were thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). Emergency treatment of hypernatremic dehydration in neonates should not choose the isotonic saline as a rehydration fluid.Conclusion: Genetic analysis presumably confirmed the diagnosis of NDI in every patient of the studied cohort. A plea of early identifying NDI confirmed by phenotype and genotype, and consequently optimize the treatment.

scholarly journals Treatment of congenital nephrogenic diabetes insipidus in pregnancy

2018 ◽  
Vol 89 (2) ◽  
pp. 112-113
Author(s):  
Agnieszka Gala-Błądzińska ◽  
Adam Mrozek ◽  
Aleksandra Kędzior ◽  
Artur Mazur ◽  
Dorota Darmochwał-Kolarz
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Congenital Nephrogenic Diabetes Insipidus ◽  
In Pregnancy
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