TRPC6 mutational analysis in Iranian children with focal segmental glomerulosclerosis

Introduction: Focal segmental glomerulosclerosis (FSGS) is a type of nephrotic syndrome which identified by edema, proteinuria, hypoalbuminemia and hyperlipidemia.TRPC6 is one of the several genes which can cause FSGS. The main aim of this study is to analyze TRPC6 in Iranian children with FSGS and evaluation the clinical features of patients with and without TRPC6 variants.Materials and Methods: twenty six patients under 16 year old were recruited. Exons 2 and 13 of TRPC6 gene were analyzed by polymerase chain reaction (PCR) amplification and sequencing.Results: The mean age of patients when sampling has been done was 9.26 ± 3.19 years (range: 2-15 years). 16 patients (61.5 %) were male and male-female ratio was 1.35:1.TRPC6 variants were identified in 4 patients (15.4 %). We identified 3 missense nonsynonymous mutation (C121S, D130V, G162R) and one missense mutation (c.333 C> T) without causing amino acid substitution (I111I).All variants were novel and in-silico analysis predicted D130V and G162R as pathogenic. There was no significant difference in following variables between patients with and without mutations: Age at disease onset, gender, hypertension, hematuria, serum creatinine and albumin, rate of progression to CRF and ESRD, consanguinity, response to steroid, resistance to cyclosporine A and cyclophosphamide.Conclusions: In this study we evaluated exons 2 and 13 of TRPC6 gene in Iranian children with FSGS. We identified four novel TRPC6 variants which two variants (D130V, G162R) by in-silico analyzing predicted as pathogenic. TRPC6 can be useful in Iranian children with FSGS for genetic screening.