Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families
- PMID: 10770218
- DOI: 10.1210/jcem.85.4.6507
Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families
Abstract
X-Linked nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by the excretion of abnormal large volumes of diluted urine mainly caused by mutations in the V2 vasopressin receptor (AVPR2) gene. By screening NDI patients for mutations within the AVPR2 gene we have identified three novel (I46K, F105V, I130F) and four recurrent (D85N, R106C, R113W, Q225X) mutations. In addition, a recurrent missense mutation (A147T) within the aquaporin-2 gene was identified in a female patient with autosomal recessive NDI associated with sensorineural deafness. Selected clinical data of the NDI patients were compared with the results from the in vitro studies. Functional analysis of I46K and I130F revealed reduced maximum agonist-induced cAMP responses as a result of an improper cell surface targeting. In contrast, the F105V mutation is delivered to the cell surface and displayed an unchanged maximum cAMP response, but impaired ligand binding abilities of F105V were reflected in a shifted concentration-response curve toward higher vasopressin concentrations. As the extracellularly located F105 is highly conserved among the vasopressin/oxytocin receptor family, functional analysis of this residue implicates an important role in high affinity agonist binding.
Similar articles
-
Molecular analyses of the vasopressin type 2 receptor and aquaporin-2 genes in Brazilian kindreds with nephrogenic diabetes insipidus.Hum Mutat. 1999;14(3):233-9. doi: 10.1002/(SICI)1098-1004(1999)14:3<233::AID-HUMU6>3.0.CO;2-O. Hum Mutat. 1999. PMID: 10477431
-
AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus.Kidney Int. 1998 Dec;54(6):1909-22. doi: 10.1046/j.1523-1755.1998.00214.x. Kidney Int. 1998. PMID: 9853256
-
Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus.J Am Soc Nephrol. 1997 Dec;8(12):1855-62. doi: 10.1681/ASN.V8121855. J Am Soc Nephrol. 1997. PMID: 9402087
-
[From genes to disease: from vasopressin-V2-receptor and aquaporine-2 to nephrogenic diabetes insipidus].Ned Tijdschr Geneeskd. 2000 Dec 9;144(50):2402-4. Ned Tijdschr Geneeskd. 2000. PMID: 11145096 Review. Dutch.
-
Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: a case report and review of the literature.Metabolism. 2012 Jul;61(7):922-30. doi: 10.1016/j.metabol.2012.01.005. Epub 2012 Mar 3. Metabolism. 2012. PMID: 22386940 Review.
Cited by
-
A novel disease-causing mutation in AVPR2: Q96H.NDT Plus. 2009 Feb;2(1):20-2. doi: 10.1093/ndtplus/sfn163. Epub 2008 Oct 31. NDT Plus. 2009. PMID: 25949277 Free PMC article.
-
Four Japanese Patients with Congenital Nephrogenic Diabetes Insipidus due to the AVPR2 Mutations.Case Rep Pediatr. 2018 Jul 3;2018:6561952. doi: 10.1155/2018/6561952. eCollection 2018. Case Rep Pediatr. 2018. PMID: 30073107 Free PMC article.
-
Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population.Mol Genet Genomic Med. 2024 Apr;12(4):e2421. doi: 10.1002/mgg3.2421. Mol Genet Genomic Med. 2024. PMID: 38622833 Free PMC article.
-
How genetic errors in GPCRs affect their function: Possible therapeutic strategies.Genes Dis. 2015 Jun;2(2):108-132. doi: 10.1016/j.gendis.2015.02.005. Genes Dis. 2015. PMID: 26229975 Free PMC article.
-
Characterization of five novel vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus reveals a role of tolvaptan for M272R-V2R mutation.Sci Rep. 2020 Oct 2;10(1):16383. doi: 10.1038/s41598-020-73089-x. Sci Rep. 2020. PMID: 33009446 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
