Academic
Publications
Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent’sJapan disease

Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent’sJapan disease,10.1046/j.1523-1755.1998.00203.x,Kidney In

Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent’sJapan disease   (Citations: 35)
BibTex | RIS | RefWorks Download
Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent'sJapan disease.BackgroundThe annual urinary screening of Japanese children above three years of age has identified a progressive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrocalcinosis, and this represents a variant of Dent's disease. Hitherto, 12 mutations of the X-linked renal specific chloride channel, CLCN5, have been reported in the Dent’sJapan variant. To further identify such CLCN5 mutations and to define the structure-function relationships of this channel, we have investigated five unrelated, non-consanguinous Japanese families with this disorder.MethodsLeukocyte DNA from probands was used with CLCN5 primers for PCR amplification of the coding region, and the DNA sequences of the products determined. Functional studies were performed by expressing the mutants in Xenopus oocytes.ResultsFive CLCN5 mutations consisting of two nonsense (R648X and R704X), two missense (S270R and L278F) and one acceptor splice site mutation (ag→cg) in intron 4 were identified. The missense and splice site mutations represent novel abnormalities. Heterologous expression in Xenopus oocytes of wild-type and the missense mutants demonstrated that the mutations, which were translated, either abolished or markedly reduced chloride conductance.ConclusionsThese results expand the spectrum of CLCN5 mutations associated with this renal disorder and provide insight into possible structure-function relationships. For example, both the missense mutations are located within a short putative loop between two transmembrane domains, and our results suggest that this region may have an important functional role in the regulation of channel activity.
Journal: Kidney International - KIDNEY INT , vol. 54, no. 6, pp. 1850-1856, 1998
Cumulative Annual
View Publication
The following links allow you to view full publications. These links are maintained by other sources not affiliated with Microsoft Academic Search.
    • ...Mutations in this gene significantly reduce or eliminate the chloride transport activity of ClC-5 [8, 9, 56]...

    Félix Claverie-Martínet al. Dent’s disease: clinical features and molecular basis

    • ...In Fig. 5 (upper panel), we show the location of only those disease-associated missense mutations in ClC-5 which have been studied with respect to their protein expression using both biochemical and functional assays [40, 57, 75, 76, 78, 106, 126]...
    • ...Interestingly, missense mutations that map close to the chloride binding sites or proton transfer sites have also been identified in ClC-1, ClC-Kb, and ClC-6 [51, 57, 68, 95, 105]...

    Leigh Wellhauseret al. ClC transporters: discoveries and challenges in defining the mechanism...

    • ...It was later detected in families from other sites, including Italy and Japan [7, 8]. Microsatellite polymorphism analysis confirmed that the families were indeed unrelated and that this is a recurrent mutation, which may represent a mutational hotspot...

    Yaacov Frishberget al. Dent’s disease manifesting as focal glomerulosclerosis: Is it the tip ...

    • ... nephrolithiasis and progressive renal failure [1, 2]. Patients show variable aminoaciduria, phosphaturia, glucosuria, kaliuresis, uricosuria, impaired urinary acidification, rickets, or osteomalacia [2, 3]. Dent’s disease and phenotypically similar disorders (X-linked recessive nephrolithiasis [4], X-linked recessive hypophosphataemic rickets [5], and the idiopathic low molecular weight proteinuria of Japanese children [6, 7]) are caused ...
    • ... aminoaciduria, phosphaturia, glucosuria, kaliuresis, uricosuria, impaired urinary acidification, rickets, or osteomalacia [2, 3]. Dent’s disease and phenotypically similar disorders (X-linked recessive nephrolithiasis [4], X-linked recessive hypophosphataemic rickets [5], and the idiopathic low molecular weight proteinuria of Japanese children [6, 7]) are caused by inactivating mutations of a renal chloride channel gene, CLCN5 [6, 8]...

    Sidharth Kumar Sethiet al. Vitamin A responsive night blindness in Dent’s disease

    • ...This triad of manifestations has been variably named in the past as X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypophosphataemic rickets or idiopathic LMW proteinuria of Japanese children [2,3]...
    • ...In addition, CLCN5 mutations have also been associated with splice sites’ disruption, as well as trafficking defects and/or Cl� /Hþ antiporter dysfunction [2,3,24]...

    Enrica Tosettoet al. Phenotypic and genetic heterogeneity in Dent's disease—the results of ...

Sort by: