Chloride channel CLCN5 mutations in Japanese children with familial idiopathic low molecular weight proteinuria

Nakazato, Hitoshi; Yoshimuta, Junichiro; Karashima, Shinnyo; Matsumoto, Shinichi; Endo, Fumio; Matsuda, Ichiro; Hattori, Shinzaburo

doi:10.1046/j.1523-1755.1999.00231.x

Cited by 22 publications

(14 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ClC-5 is found in the S 2 and S 3 segments of proximal tubules, mainly in immediately early endosomes (30)(31)(32)(33)(34)(35). Also, Devuyst et al (35) demonstrated that proximal tubule cells transfected with ClC-5 are able to endocytose albumin and that the channel colocalizes with the albumin present in the endosomes.…”

Section: Clc-5 Chloride Channel and Protein Endocytosismentioning

confidence: 99%

“…Many of them have explored and characterized the mutations responsible for the several variants of XLN (20,21,26,28,30,(56)(57)(58)(59). Very few papers have focused on the physiological role and regulation of this channel (35,47,49).…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

“…Although ClC-5 may have a structure and function pattern similar to that of other members of the family, such studies have not been done on ClC-5. Similar studies are necessary because they could help clarify why different mutations of ClCN5 may result in such different phenotypes (20,21,26,28,30,(56)(57)(58)(59)(60).…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

“…However, the rickety phenotype is common in Europe (20,21,26,27,30,(57)(58)(59). Recent data suggest a role of ClC-5 in calcium metabolism (47,52).…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

See 3 more Smart Citations

ClC-5 chloride channel and kidney stones: what is the link?

Silva

Morales

Lopes

2001

Braz J Med Biol Res

View full text Add to dashboard Cite

Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/ or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.

show abstract

Section: Clc-5 Chloride Channel and Protein Endocytosismentioning

confidence: 99%

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

“…However, the rickety phenotype is common in Europe (20,21,26,27,30,(57)(58)(59). Recent data suggest a role of ClC-5 in calcium metabolism (47,52).…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

See 2 more Smart Citations

ClC-5 chloride channel and kidney stones: what is the link?

Silva

Morales

Lopes

2001

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…Thus far, nine different mammalian chloride channels (CLC), including CLC-K1, CLC-K2, and CLC-1 to CLC-7, have been identified (1, 4, 15, 16, 18, 19, 30, 36 -38, 40). Mutations of different chloride channels have been linked to a range of clinical conditions including CLC-1 in myotonia congenita, CLCNKB (human gene for CLC-K2) in Bartter's syndrome, and CLC-5 in Dent's disease, X-linked recessive nephrolithiasis (XLRN), X-linked recessive hypophosphatemic rickets, and low-molecular-weight (LMW) proteinuria/nephrocalcinosis (21,26,28,34,38). Clinical features reported among patients afflicted with various inactivating CLC-5 mutations include varying degrees of LMW proteinuria, hypercalciuria, hyperphosphaturia, nephrocalcinosis, nephrolithiasis, urinary concentrating defect, and renal failure.…”

mentioning

confidence: 99%

Hypertonicity increases CLC-5 expression in mouse medullary thick ascending limb cells

Pham¹,

Devuyst²,

Pham³

et al. 2004

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

gawa, and Adam M. Sun. Hypertonicity increases CLC-5 expression in mouse medullary thick ascending limb cells. Am J Physiol Renal Physiol 287: F747-F752, 2004. First published May 25, 2004 10.1152/ajprenal.00229.2003.-Genetic studies indicated that mutations of the chloride channel CLC-5 in the kidney are responsible for a group of clinical disorders, collectively called Dent's disease. In the kidney, CLC-5 was found to be expressed in the proximal tubule, medullary thick ascending limb (mTAL) of loop of Henle, and intercalated cells of the collecting tubule. In proximal tubular cells, CLC-5 was found to play an important role in receptor-mediated endocytosis. However, the functional roles of CLC-5 in mTAL and collecting tubules remain unclear. Because mTAL is normally exposed to a hypertonic environment, we aimed to examine the effect of hypertonicity on CLC-5 expression in this nephron segment. Our studies revealed that exposure to hypertonicity (up to 550 mosM) increased CLC-5 mRNA and protein levels in a murine mTAL cell line (MTAL) but not in an opossum kidney (OK) proximal tubular cell line. A similar effect was also found in mouse kidneys, where CLC-5 expression was enhanced in renal medulla, but not cortex, after 48 h of water deprivation. We also tested the effect of hypertonicity on endocytotic activity and found that exposure to hypertonicity caused a significant decrease in cellular uptake of FITC-labeled albumin in OK but not in MTAL cells. Our results suggest that CLC-5 expression is upregulated by hypertonicity in mTAL cells but not in proximal tubular cells. We speculate that the increased CLC-5 levels in mTAL may serve to maintain the endocytotic activity in a hypertonic environment.

show abstract

Mutation Update of theCLCN5Gene Responsible for Dent Disease 1

et al. 2015

View full text Add to dashboard Cite

Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1. Herein, we review previously reported mutations (n = 192) and their associated phenotype in 377 male patients with Dent disease 1 and describe phenotype and novel (n = 42) and recurrent mutations (n = 24) in a large cohort of 117 Dent disease 1 patients belonging to 90 families. The novel missense and in-frame mutations described were mapped onto a three-dimensional homology model of the ClC-5 protein. This analysis suggests that these mutations affect the dimerization process, helix stability, or transport. The phenotype of our cohort patients supports and extends the phenotype that has been reported in smaller studies.

show abstract

Chloride channel CLCN5 mutations in Japanese children with familial idiopathic low molecular weight proteinuria

Abstract: We conclude that the CLCN5 gene is responsible for the renal proximal tubulopathy in many Japanese families and suggest that molecular defects, environmental factors, or other modifying genes may account for the different phenotypes.

Cited by 22 publications

References 18 publications

ClC-5 chloride channel and kidney stones: what is the link?

ClC-5 chloride channel and kidney stones: what is the link?

Hypertonicity increases CLC-5 expression in mouse medullary thick ascending limb cells

Mutation Update of theCLCN5Gene Responsible for Dent Disease 1

Contact Info

Product

Resources

About