A novel TRPC6 mutation in a family with podocytopathy and clinical variability ; BMC Nephrol

Background ; Mutation in several podocyte-specific genes have been noted to result in phenotypic heterogeneity. Herein, we report a novel, autosomal dominant TRPC6 mutation in a family with disease ranging from asymptomatic minimal change disease to end-stage kidney disease. ; Case presentation ; A 35 year old woman developed asymptomatic, nephrotic range proteinuria during pregnancy that did not resolve after delivery. Her mother had end-stage kidney disease of unknown etiology and her brother had asymptomatic proteinuria. Kidney biopsy revealed minimal change disease in both the proband and her brother. Genetic testing was performed in the proband and mother, revealing a novel frameshift mutation in TRPC6, D873fsX878. The proband continues to have subnephrotic range proteinuria and normal creatinine but her brother has since developed progressive chronic kidney disease. ; Conclusions ; The current case report underscores the heterogeneity of disease in podocytopathies and related genes. Genetic testing of podocyte genes is useful in order to understand the pathophysiologic processes underlying these overlapping diseases. ; 1K23DK093804-01/DK/NIDDK NIH HHS/United States ; 1U18DP002708-01/DP/NCCDPHP CDC HHS/United States ; 5-U01HG006487-02/HG/NHGRI NIH HHS/United States ; 5-UL1RR025747-04/RR/NCRR NIH HHS/United States ; 23663351 ; PMC3662586