Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients

Chen, Chia‐Hsiang; Chen, Wenyu; Liu, Huilin; Liu, Tze-Tze; Tsou, Ann-Ping; Lin, Ching‐Yuang; Chao, Ting‐Hsing; Qi, Yu; Hsiao, Kwang-Jen

doi:10.1007/s100380200002

Cited by 28 publications

(10 citation statements)

References 16 publications

(20 reference statements)

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“…Two patients with p.R106C reported by Pasel et al [ 14 ] had high basal urine osmolality and partial response to AVP administration. Chen et al [ 15 ] also reported that an NDI patient with p.R106C had normal urine and plasma osmolality and plasma electrolytes, similar to our patient (Case 2).…”

Section: Discussionsupporting

confidence: 84%

“…The mutations p.K100KfsX91 and p.W99X produced a premature stop codon, resulting in a truncated protein. Regarding p.R106C, that mutation was identified in 7.7% (5/65) of Japanese NDI patients [ 17 ] and also was identified in other Asian and ethnic populations [ 2 , 12 , 15 , 16 ]. The p.R106C mutation occurs at CpG nucleotides, which are mutation hot spots for genetic diseases.…”

Section: Discussionmentioning

confidence: 99%

“…As a previous in vitro study showed that p.R106C retained a slight capacity for production of cAMP in response to AVP, p.R106C is thought to cause less severe NDI [ 15 ]. Two patients with p.R106C reported by Pasel et al [ 14 ] had high basal urine osmolality and partial response to AVP administration.…”

Section: Discussionmentioning

confidence: 99%

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Four Japanese Patients with Congenital Nephrogenic Diabetes Insipidus due to theAVPR2Mutations

Namatame-Ohta

Morikawa

Nakamura

et al. 2018

Case Reports in Pediatrics

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Almost 90% of nephrogenic diabetes insipidus (NDI) is caused by mutations in the arginine vasopressin receptor 2 gene (AVPR2) on the X chromosome. Herein, we reported clinical and biochemical parameters in four cases of three unrelated Japanese families and analyzed the status of the AVPR2. Two of the four patients had poor weight gain. However, in the male and female sibling cases, neither had poor weight gain while toddlers, but in the male sibling, episodes of recurrent fever, polyuria, and polydipsia led to the diagnosis of NDI at 4 years of age. Analysis of AVPR2 identified two nonsense mutations (c.299_300insA; p.K100KfsX91 and c.296G > A; p.W99X) and one missense mutation (c.316C > T; p.R106C). These mutations were previously reported. The patient with c.316C > T; p.R106C had milder symptoms consistent with previous reports. Of the familial cases, the sister was diagnosed as having NDI, but a skewed X-inactivation pattern in her peripheral blood lymphocytes was not identified. In conclusion, our study expands the spectrum of phenotypes and characterized mutations in AVPR2 in NDI.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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Four Japanese Patients with Congenital Nephrogenic Diabetes Insipidus due to theAVPR2Mutations

Namatame-Ohta

Morikawa

Nakamura

et al. 2018

Case Reports in Pediatrics

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“…Of these, only 7 mutations causing partial NDI have been previously reported [7,8,9,10,11,12,13]. Most AVPR2 mutations are missense mutations that disrupt receptor function at various levels, such as intracellular receptor retention, defects in ligand binding or defects in G protein coupling and activation [14].…”

Section: Introductionmentioning

confidence: 99%

Functional Characterization of Vasopressin Receptor 2 Mutations Causing Partial and Complete Congenital Nephrogenic Diabetes Insipidus in Thai Families

Sahakitrungruang

Tee²,

Rattanachartnarong³

et al. 2010

Horm Res Paediatr

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Background:AVPR2 mutations cause most cases of nephrogenic diabetes insipidus (NDI); 211 AVPR2 mutations have been described, but only 7 are described causing partial NDI. Methods: Two unrelated Thai boys had polyuria and polydipsia in infancy but had normal electrolytes and serum osmolality at 2 years of age. Patient 1 could not concentrate his urine in response to water deprivation or 1-desamino-8-D-arginine vasopressin (DDAVP); patient 2 could concentrate to ∼600 mosm/l. The patients’ AVPR2 genes were sequenced and the identified mutations were re-created in AVPR2 cDNA expression vectors. AVPR2 activities were measured by stimulating transfected HEK293T cells with arginine vasopressin (AVP) or DDAVP, and assessing the resulting cAMP production by the activation of a luciferase reporter. Results: Patient 1 carried the previously described missense mutation R181C; patient 2 carried the novel missense mutation M311V. When transiently transfected into HEK293T cells, 6.8 × 10^–12 M AVP induced the half-maximal response (EC50) of the wild-type, whereas the EC50 value for R181C was 5.9 × 10^–9 M and for M311V was 2.6 × 10^–10M. Responses to DDAVP were qualitatively similar but required 10-fold higher concentrations. Conclusion: The novel AVPR2 mutation M311V retains partial activity and results in a milder form of NDI.

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“…NDI manifests in three forms, namely X-linked, autosomal dominant, and autosomal recessive [88]. X-linked NDI is due to mutations in the arginine vasopressin 2 receptor, which initiates hAQP2 expression and trafficking to the plasma membrane when bound to arginine vasopressin [89][90][91][92]. Autosomal NDI is due to point mutations in hAQP2.…”

Section: Introductionmentioning

confidence: 99%

Improved Protocol for the Production of the Low-Expression Eukaryotic Membrane Protein Human Aquaporin 2 in Pichia pastoris for Solid-State NMR

et al. 2020

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Solid-state nuclear magnetic resonance (SSNMR) is a powerful biophysical technique for studies of membrane proteins; it requires the incorporation of isotopic labels into the sample. This is usually accomplished through over-expression of the protein of interest in a prokaryotic or eukaryotic host in minimal media, wherein all (or some) carbon and nitrogen sources are isotopically labeled. In order to obtain multi-dimensional NMR spectra with adequate signal-to-noise ratios suitable for in-depth analysis, one requires high yields of homogeneously structured protein. Some membrane proteins, such as human aquaporin 2 (hAQP2), exhibit poor expression, which can make producing a sample for SSNMR in an economic fashion extremely difficult, as growth in minimal media adds additional strain on expression hosts. We have developed an optimized growth protocol for eukaryotic membrane proteins in the methylotrophic yeast Pichia pastoris. Our new growth protocol uses the combination of sorbitol supplementation, higher cell density, and low temperature induction (LT-SEVIN), which increases the yield of full-length, isotopically labeled hAQP2 ten-fold. Combining mass spectrometry and SSNMR, we were able to determine the nature and the extent of post-translational modifications of the protein. The resultant protein can be functionally reconstituted into lipids and yields excellent resolution and spectral coverage when analyzed by two-dimensional SSNMR spectroscopy.

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Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients

Cited by 28 publications

References 16 publications

Four Japanese Patients with Congenital Nephrogenic Diabetes Insipidus due to theAVPR2Mutations

Four Japanese Patients with Congenital Nephrogenic Diabetes Insipidus due to theAVPR2Mutations

Functional Characterization of Vasopressin Receptor 2 Mutations Causing Partial and Complete Congenital Nephrogenic Diabetes Insipidus in Thai Families

Improved Protocol for the Production of the Low-Expression Eukaryotic Membrane Protein Human Aquaporin 2 in Pichia pastoris for Solid-State NMR

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