| Autor: |
E, Tosetto, F, Anglani, R, Graziotto, L, Citron, A, D'Angelo, G, Gambaro |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. 20(6) |
| ISSN: |
0393-5590 |
| Popis: |
Dent's disease, a X-linked hypercalciuric nephrolithiasis, is caused by mutations of the CLCN5 gene. The disease is characterised by low molecular weight proteinuria with variable presence of hypercalciuria, hyperphosphaturia, nephrocalcinosis, and kidney stones. CLCN5 encodes a chloride channel belonging to the voltage-gated chloride channel family, which is predominantly expressed in the endosomes of proximal tubular cells. By shunting the current of electrogenic H+-ATPase, ClC-5 is crucial for efficient acidification of renal endosomes. As shown in knock-out mouse models, the ClC-5 loss of function causes severe impairment of receptor-mediated endocytosis, as well as the endocytotic retrieval of plasma membrane proteins including megalin. In a minority of patients with classical Dent's disease, the analysis of CLCN5 coding sequences failed to identify causative mutations. It is conceivable that mutations in the 5' upstream regulatory regions could impair the correct processing and translation of CLCN5. The complexity of its promoter region seems to support this hypothesis. Molecular diagnosis of Dent's disease is now available; since the risk of developing renal insufficiency in adult life is elevated for this type of nephrolithiasis, the correct diagnosis could potentially modify the natural history of the disease by preventing the evolution towards uraemia. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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