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Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families.
Horm Res Paediatr. 2010; 73(5):349-54.HR

Abstract

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 approximately 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 x 10(-12) M AVP induced the half-maximal response (EC50) of the wild-type, whereas the EC50 value for R181C was 5.9 x 10(-9) M and for M311V was 2.6 x 10(-10)M. 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.

Authors+Show Affiliations

Division of Pediatric Endocrinology, Chulalongkorn University, Bangkok, Thailand.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20389105

Citation

Sahakitrungruang, Taninee, et al. "Functional Characterization of Vasopressin Receptor 2 Mutations Causing Partial and Complete Congenital Nephrogenic Diabetes Insipidus in Thai Families." Hormone Research in Paediatrics, vol. 73, no. 5, 2010, pp. 349-54.
Sahakitrungruang T, Tee MK, Rattanachartnarong N, et al. Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families. Horm Res Paediatr. 2010;73(5):349-54.
Sahakitrungruang, T., Tee, M. K., Rattanachartnarong, N., Shotelersuk, V., Suphapeetiporn, K., & Miller, W. L. (2010). Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families. Hormone Research in Paediatrics, 73(5), 349-54. https://doi.org/10.1159/000308167
Sahakitrungruang T, et al. Functional Characterization of Vasopressin Receptor 2 Mutations Causing Partial and Complete Congenital Nephrogenic Diabetes Insipidus in Thai Families. Horm Res Paediatr. 2010;73(5):349-54. PubMed PMID: 20389105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families. AU - Sahakitrungruang,Taninee, AU - Tee,Meng Kian, AU - Rattanachartnarong,Natthakorn, AU - Shotelersuk,Vorasuk, AU - Suphapeetiporn,Kanya, AU - Miller,Walter L, Y1 - 2010/04/14/ PY - 2009/02/11/received PY - 2009/07/09/accepted PY - 2010/4/15/entrez PY - 2010/4/15/pubmed PY - 2010/7/16/medline SP - 349 EP - 54 JF - Hormone research in paediatrics JO - Horm Res Paediatr VL - 73 IS - 5 N2 - 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 approximately 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 x 10(-12) M AVP induced the half-maximal response (EC50) of the wild-type, whereas the EC50 value for R181C was 5.9 x 10(-9) M and for M311V was 2.6 x 10(-10)M. 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. SN - 1663-2826 UR - https://www.unboundmedicine.com/medline/citation/20389105/Functional_characterization_of_vasopressin_receptor_2_mutations_causing_partial_and_complete_congenital_nephrogenic_diabetes_insipidus_in_Thai_families_ L2 - https://www.karger.com?DOI=10.1159/000308167 DB - PRIME DP - Unbound Medicine ER -