Van gen naar ziekte; de ziekte van Dent veroorzaakt door afwijkingen in CLCN5- en OCRL1-genen

Dent's disease is an X-linked disorder, characterized by generalized proximal tubular dysfunction, nephrolithiasis, nephrocalcinosis and the development of end-stage renal disease, generally occurring after the age of thirty. In the majority of cases, the disease is caused by mutations in the CLCN5-gene. The pathogenesis of the disease has not yet been clarified. Defective recycling of multi-ligand proximal tubular receptors megalin and cubilin is considered responsible for the defective reabsorption of low molecular weight proteins, albumin, hormones and vitamins. Treatment with thiazide diuretics to diminish the hypercalciuria in combination with citrate supplements might prevent renal stone formation and deterioration of renal function. In the laboratory of DNA diagnostics in the Radboud University Nijmegen Medical Centre, the molecular analysis of the CLCN5-gene in patients suspected with this disease is performed.