A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers

Schernthaner-Reiter, Marie Helene; Adams, David R.; Trivellin, Giampaolo; Ramnitz, Mary Scott; Raygada, Margarita; Golas, Gretchen; Faucz, Fábio R.; Nilsson, Ola; Nella, Aikaterini A.; Dileepan, Kavitha; Lodish, Maya; Lee, Paul; Tifft, Cynthia J.; Markello, Thomas C.; Gahl, William A.; Stratakis, Constantine A.

doi:10.1007/s00431-015-2684-4

Cited by 12 publications

(10 citation statements)

References 14 publications

(18 reference statements)

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“…For underage patients, low-salt diet and reasonable protein diet are necessary to maintain growth and development [Bockenhauer and Bichet, 2015]. The traditional medicine for NDI are thiazide diuretics and a high concentra-tion of desmopressin [Konoshita et al, 2004;Sung and Lin, 2011;Schernthaner-Reiter et al, 2016]. In our study, the proband accepted the hydrochlorothiazide (25 mg/ day) treatment, and the urine volume reduced to 2500 mL per day.…”

Section: Discussionmentioning

confidence: 75%

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

et al. 2020

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Loss of function of arginine vasopressin receptor 2 (AVPR2) may affect the recognition and binding of arginine vasopressin (AVP) which, in turn, may prevent the activation of Gs/ adenylate cyclase and reduce the reabsorption of water by renal tubules and combined tubes. Finally, the organism may suffer from nephrogenic diabetes insipidus (NDI), a kind of kidney disorder featured by polyuria and polydipsia, due to a break of water homeostasis. In this study, we enrolled a Chinese family with polyuria and polydipsia. The proband presented abnormal fluid intake and excessive urine output. A water deprivation and AVP stimulation test further indicated that this patient had NDI. By sequencing known causative genes for diabetes insipidus, we identified a novel mutation in AVPR2 (c.547G>A; p.V183M) in the family. This mutation, located in a conserved site of AVPR2 and predicted to be disease-causing by informatics programs, was absent in our 200 controls and other public databases. Our study not only further confirms the clinical diagnosis, but also expands the spectrum of AVPR2 mutations and contributes to genetic diagnosis and counseling of patients with NDI.

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Section: Discussionmentioning

confidence: 75%

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

et al. 2020

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“…One possible explanation for this discrepancy is that our result is based on cell-based characterization of the GGCX-Δex3 mutant. However the patients’ splice-site mutation (c.373+3G>T) may not completely abolish normal processing of the GGCX pre-mRNA, and this could produce a portion of correctly processed mRNA for translating the functional protein, as has been reported in other diseases (Mikkola et al , 1997; Schernthaner-Reiter et al , 2016). It is also possible that this splice-site mutation could result in several variant mRNA transcripts of GGCX, as has previously described for other genes (Gallinaro et al , 2006; Kallabi et al , 2015).…”

Section: To the Editormentioning

confidence: 96%

“…Mutations in exon-intron junctions could lead to mis-splicing and could result in exon skipping, activation of a cryptic splice-site, or intron retention. Importantly, a single splice-site mutation can result in multiple mRNA transcripts and can affect the protein function (Gallinaro et al , 2006; Kallabi et al , 2015; Mikkola et al , 1997; Schernthaner-Reiter et al , 2016). Therefore, it is important to clarify the effect of the GGCX splicing-site mutation (c.373+3G>T) on the splicing mechanism and the possible GGCX mRNA transcripts in these affected patients, especially when mutations in the causative gene for the classical PXE syndrome have been excluded.…”

Section: To the Editormentioning

confidence: 99%

Splice-Site Mutation of Exon 3 Deletion in the Gamma-Glutamyl Carboxylase Gene Causes Inactivation of the Enzyme

Jin

Vermeer

Stafford

et al. 2016

Journal of Investigative Dermatology

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“…[3] To date, more than 220 AVPR2 variants have been recognized to cause X-linked NDI. [10] Missense mutations can lead to partially preserved receptor expression and function and hence a milder diabetes insipidus. [11]…”

Section: Introductionmentioning

confidence: 99%

A novel AVPR2 missense mutation in an Asian family with inherited nephrogenic diabetes insipidus

Zhang

Chen

et al. 2019

Medicine

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Rationale:X-linked nephrogenic diabetes insipidus (NDI) is a rare inherited disease, and is characterized by renal resistance to arginine vasopressin (AVP). Its diagnosis can be clinically challenging. The application of molecular genetic analysis can provide a rapid and definitive diagnosis.Patient concerns:A 75-year-old woman presented with recurrent nausea and vomiting was admitted to the Department of Gastroenterology. The patient had a strong family history of polydipsia and polyuria. Sequencing analysis of the antidiuretic hormone arginine vasopressin receptor 2 (AVPR2) revealed the novel missense mutation p. Trp164Cys (c.492G>G/C) in exon 2. There was a heterozygous mutation in the patient's sister and niece, while there was a mutation in her sons, brother and nephews. The locus is located on the X chromosome Xq28, and its mutation can lead to X linked recessive NDI. The p. Trp164Cys mutation of AVPR2 gene has not been reported in literature before. The mutation was predicted to be probably damaging by several prediction methods, including SIFT and PolyPhen-2. There was no significant abnormal variation in other detection regions of the gene. And there was also no abnormal variation in AVP and AQP2 genes in this family.Diagnosis:X-linked NDI was diagnosed according to the patient's family history and DNA sequencing analysis.Interventions and outcomes:After treated with desmopressin, antiemetic drugs and massive infusion glucose transfusion, the patient's urine volume decreased and electrolyte disturbance was corrected, and the symptoms of nausea and vomiting gradually disappeared.Lessons:The patients with suspected congenital NDI should undergo genetic sequencing analysis of AVPR2, AVP and AQP2 genes. A definitive diagnosis can benefit patient and avoid unnecessary investigations.

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A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers

Cited by 12 publications

References 14 publications

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

Splice-Site Mutation of Exon 3 Deletion in the Gamma-Glutamyl Carboxylase Gene Causes Inactivation of the Enzyme

A novel AVPR2 missense mutation in an Asian family with inherited nephrogenic diabetes insipidus

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