Blood filtration and formation of primary urine in the kidney glomerulus is provided by a specialized membrane called slit diaphragm located between well-branched pedicels of podocytes. Actually, the slit diaphragm is a protein supercomplex, whose disruption can cause failure of renal filtration, and patients usually manifest nephrotic syndrome. Recently, familial forms of nephrotic syndrome have been described which arise from malfunction of mutated proteins making up the slit diaphragm. In 2005 it was found that one of the proteins present in this complex was non-selective cation channel TRPC6. The aim of this work was to screen mutations and polymorphisms of the TRPC6 gene in a group of 64 Czech patients with nephrotic syndrome and subsequently, on the basis of these data, evaluate the role of mutations in the TRPC6 gene in Czech population. The analysis was performed by the PCR method followed by direct sequencing and high-resolution melting method. We have not identified any mutations in our group of patients. Two additional single nucleotide polymorphisms – p.P15S and p.A404V – were detected along with nucleotide changes that did not result in amino acid changes and with a few intronic changes. P.P15S heterozygotes were more frequent in patients with steroid-resistant FSGS than in steroid- sensitive patients (29 % versus 12.1 %). To conclude, we did not find any probable disease-causing mutation in the TRPC6 gene in the cohort of 64 Czech patients. The p.P15S polymorphism might have some influence on the therapeutic response of FSGS patients.

Department of Nephrology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

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