Background: In steroid-resistant nephrotic syndrome (SRNS), a considerable number of patient progress to end-stage renal disease (ESRD), despite aggressive therapy. The latest advance in familial focal segmental glomerulosclerosis (FSGS) has been the discovery of a mutant form of canonical transient receptor potential channel 6 (TRPC6) leading to FSGS through unclear mechanisms. The aim of this study is to screen for TRPC6 mutations in familial and sporadic SRNS patients.
Methods: Twenty-five children with SRNS originating from Turkey were included in this study. Nine patients had familial and 16 patients had sporadic SRNS. Mutation analysis was performed in all 13 coding exons of the TRPC6 gene with the direct DNA sequencing method. The control group consisted of 50 normal healthy children originating from Turkey.
Results: No mutation was detected in nine children (four familial, five sporadic). A variant (L395A) in one patient, intronic nucleotide substitution (c.171 + 16 A>G and c.171 + 86 G>C) in six patients and previously described missense (A404V; rs36111323) and synonymous (N561N; rs12366144) aminoacid variants in nine patients were found. Among patients with intronic, missense and synonymous aminoacid variants, 5 patients had familial and 11 patients had sporadic SRNS. Their mean age at onset of proteinuria was 2.6 ± 1.7 years. Seven cases (three familial, four sporadic) progressed to ESRD with a mean time of 10.2 ± 2.9 years.
Conclusions: In conclusion, analysis of TRPC6 gene mutations in FSGS will provide new insights into the pathogenesis of nephrotic syndrome. Previous works have emphasized that the patients with only hereditary familial FSGS carried a missense mutation in the TRPC6 gene. Our findings suggest that TRPC6 mutations may also have an important role in the pathogenesis of sporadic SRNS.